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Dr. MARTA ALONSO-HEARN
Department of Animal Health, NEIKER-Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain

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0 Cattle
0 Genetics
0 Genomics
0 Host-pathogen Interactions
0 Immunology

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paratuberculosis
Cattle
Macrophages
Mycobacteria
Vaccines
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Bovine tuberculosis

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Preprint content
Published: 09 July 2021
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Bovine paratuberculosis (PTB), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis that affects cattle worldwide. According to their severity and extension, PTB-associated histological lesions have been classified into the following groups; focal, multifocal, and diffuse. It is unknown whether these lesions represent sequential stages or divergent outcomes. In the current study, the associations between host genetics and pathology were explored by genotyping 813 Spanish Holstein cows with no visible lesions (N= 373) and with focal (N=371), multifocal (N=33), and diffuse (N=33) lesions in gut tissues and regional lymph nodes. DNA from peripheral blood samples of these animals was genotyped with the Bovine EuroG MD Bead Chip, and the corresponding genotypes were imputed to whole-genome sequencing (WGS) data using the 1,000 Bull genomes reference population. A genome-wide association study (GWAS) was performed using the WGS data and the presence or absence of each type of histological lesion in a case-control approach. No overlap was seen in the SNPs controlling the three PTB-associated lesions. A total of 192 and 92 SNPs defining 13 and 9 distinct quantitative trait loci (QTLs) were highly-associated (P ≤ 5 x 10-7) with the multifocal (heritability= 0.075) and the diffuse (heritability= 0.189) lesions, respectively. Some of the identified QTLs overlapped with QTLs previously associated with PTB, bovine tuberculosis, mastitis, and IgG levels. Pathway analysis with candidate genes overlapping the identified QTLs revealed a significant enrichment of the keratinization pathway and cholesterol metabolism in the animals with multifocal and diffuse lesions, respectively. While keratin variants may predispose cows to the development of multifocal lesions, cholesterol variants associate with the more severe lesions. Taken together, these findings suggest that the variation in MAP-associated pathological outcomes might be genetically determined and indicative of distinct host responses in genetically predisposed individuals.

ACS Style

Maria Canive; Gerard Badia-Bringué; Patricia Vázquez; Oscar González-Recio; Almudena Fernandez; Joseba M. Garrido; Ramón A. Juste; Marta Alonso-Hearn. Host Genetics Underlying Pathological Outcomes to Mycobacterium Avium Subsp. Paratuberculosis Infection is Governed by Distinct Genetic Variants. 2021, 1 .

AMA Style

Maria Canive, Gerard Badia-Bringué, Patricia Vázquez, Oscar González-Recio, Almudena Fernandez, Joseba M. Garrido, Ramón A. Juste, Marta Alonso-Hearn. Host Genetics Underlying Pathological Outcomes to Mycobacterium Avium Subsp. Paratuberculosis Infection is Governed by Distinct Genetic Variants. . 2021; ():1.

Chicago/Turabian Style

Maria Canive; Gerard Badia-Bringué; Patricia Vázquez; Oscar González-Recio; Almudena Fernandez; Joseba M. Garrido; Ramón A. Juste; Marta Alonso-Hearn. 2021. "Host Genetics Underlying Pathological Outcomes to Mycobacterium Avium Subsp. Paratuberculosis Infection is Governed by Distinct Genetic Variants." , no. : 1.

Journal article
Published: 12 May 2021 in Animals
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Paratuberculosis (PTB), a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), is responsible for important economic losses in the dairy industry. Our previous RNA-sequencing (RNA-Seq) analysis showed that bovine intelectin 2 (ITLN2) precursor gene was overexpressed in ileocecal valve (ICV) samples of animals with focal (log2 fold-change = 10.6) and diffuse (log2 fold-change = 6.8) PTB-associated lesions compared to animals without lesions. This study analyzes the potential use of ITLN2, a protein that has been described as fundamental in the innate immune response to infections, as a biomarker of MAP infection. The presence of ITLN2 was investigated by quantitative immunohistochemical analysis of ICV samples of 20 Holstein Friesian cows showing focal (n = 5), multifocal (n = 5), diffuse (n = 5) and no histological lesions (n = 5). Significant differences were observed in the mean number of ITLN2 immunostained goblet and Paneth cells between the three histopathological types and the control. The number of immunolabelled cells was higher in the focal histopathological type (116.9 ± 113.9) followed by the multifocal (108.7 ± 140.5), diffuse (76.5 ± 97.8) and control types (41.0 ± 81.3). These results validate ITLN2 as a post-mortem biomarker of disease progression.

ACS Style

Cristina Blanco Vázquez; Ana Balseiro; Marta Alonso-Hearn; Ramón Juste; Natalia Iglesias; Maria Canive; Rosa Casais. Bovine Intelectin 2 Expression as a Biomarker of Paratuberculosis Disease Progression. Animals 2021, 11, 1370 .

AMA Style

Cristina Blanco Vázquez, Ana Balseiro, Marta Alonso-Hearn, Ramón Juste, Natalia Iglesias, Maria Canive, Rosa Casais. Bovine Intelectin 2 Expression as a Biomarker of Paratuberculosis Disease Progression. Animals. 2021; 11 (5):1370.

Chicago/Turabian Style

Cristina Blanco Vázquez; Ana Balseiro; Marta Alonso-Hearn; Ramón Juste; Natalia Iglesias; Maria Canive; Rosa Casais. 2021. "Bovine Intelectin 2 Expression as a Biomarker of Paratuberculosis Disease Progression." Animals 11, no. 5: 1370.

Journal article
Published: 11 January 2021 in Scientific Reports
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Although genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP) infection, only a few functional mutations for bovine paratuberculosis (PTB) have been characterized. Expression quantitative trait loci (eQTLs) are genetic variants typically located in gene regulatory regions that alter gene expression in an allele-specific manner. eQTLs can be considered as functional links between genomic variants, gene expression, and ultimately phenotype. In the current study, peripheral blood (PB) and ileocecal valve (ICV) gene expression was quantified by RNA-Seq from fourteen Holstein cattle with no lesions and with PTB-associated histopathological lesions in gut tissues. Genotypes were generated from the Illumina LD EuroG10K BeadChip. The associations between gene expression levels (normalized read counts) and genetic variants were analyzed by a linear regression analysis using R Matrix eQTL 2.2. This approach allowed the identification of 192 and 48 cis-eQTLs associated with the expression of 145 and 43 genes in the PB and ICV samples, respectively. To investigate potential relationships between these cis-eQTLs and MAP infection, a case–control study was performed using the genotypes for all the identified cis-eQTLs and phenotypical data (histopathology, ELISA for MAP-antibodies detection, tissue PCR, and bacteriological culture) of 986 culled cows. Our results suggested that the heterozygous genotype in the cis-eQTL-rs43744169 (T/C) was associated with the up-regulation of the MDS1 and EVI1 complex (MECOM) expression, with positive ELISA, PCR, and bacteriological culture results, and with increased risk of progression to clinical PTB. As supporting evidence, the presence of the minor allele was associated with higher MECOM levels in plasma samples from infected cows and with increased MAP survival in an ex-vivo macrophage killing assay. Moreover, the presence of the two minor alleles in the cis-eQTL-rs110345285 (C/C) was associated with the dysregulation of the eukaryotic elongation factor 1-α2 (eEF1A2) expression and with increased ELISA (OD) values. Finally, the presence of the minor allele in the cis-eQTL rs109859270 (C/T) was associated with the up-regulation of the U1 spliceosomal RNA expression and with an increased risk of progression to clinical PTB. The introduction of these novel functional variants into marker-assisted breeding programs is expected to have a relevant effect on PTB control.

ACS Style

Maria Canive; Nora Fernandez-Jimenez; Rosa Casais; Patricia Vázquez; José Luis Lavín; José Ramón Bilbao; Cristina Blanco-Vázquez; Joseba M. Garrido; Ramón A. Juste; Marta Alonso-Hearn. Identification of loci associated with susceptibility to bovine paratuberculosis and with the dysregulation of the MECOM, eEF1A2, and U1 spliceosomal RNA expression. Scientific Reports 2021, 11, 1 -14.

AMA Style

Maria Canive, Nora Fernandez-Jimenez, Rosa Casais, Patricia Vázquez, José Luis Lavín, José Ramón Bilbao, Cristina Blanco-Vázquez, Joseba M. Garrido, Ramón A. Juste, Marta Alonso-Hearn. Identification of loci associated with susceptibility to bovine paratuberculosis and with the dysregulation of the MECOM, eEF1A2, and U1 spliceosomal RNA expression. Scientific Reports. 2021; 11 (1):1-14.

Chicago/Turabian Style

Maria Canive; Nora Fernandez-Jimenez; Rosa Casais; Patricia Vázquez; José Luis Lavín; José Ramón Bilbao; Cristina Blanco-Vázquez; Joseba M. Garrido; Ramón A. Juste; Marta Alonso-Hearn. 2021. "Identification of loci associated with susceptibility to bovine paratuberculosis and with the dysregulation of the MECOM, eEF1A2, and U1 spliceosomal RNA expression." Scientific Reports 11, no. 1: 1-14.

Journal article
Published: 30 June 2020 in Heliyon
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Little is known about the correlations between the genetic susceptibility/resistance to Mycobacterium avium subsp. paratuberculosis (Map) infection and the estimated breeding values for type, production and functional traits. Previously, we identified 70 combinations of five single nucleotide polymorphisms (SNPs) in four bovine innate immune genes (SLC11A1, SP110, TLR2, CD209) that are associated with the genetic risk of paratuberculosis (PTB) or Johne's disease progression, which can be graded as low (LOWIN), latent (LATIN), or patent (PATIN) risk. Other possible combinations of these 5 SNPs were grouped in the average group (AVERIN). In the current study, differences in estimated breeding values (EBVs) for several traits were analyzed using linear models in a large cohort of Holstein cows (N = 15656) genotyped across Spain in 2016 or 2017. After the assignment of each genotyped cow to a risk group, cows within the PATIN risk group (N = 1448) had a superior combined genetic index (2797.57), type genetic index (524.62), milk yield (653.92 kg), protein yield (21.77 kg), fat yield (24.82 kg) and economic merit index (125 Euros) compared with the other three risk groups. Statistically significant differences in the longevity scores between the cows that were included in the PATIN risk group (108.85) and the LOWIN (107.82) and AVERIN (107.92) groups were also observed. The associations between the genetic risk groups and PTB diagnostic results were validated in a population of 99 cows from a Spanish farm with a high prevalence of PTB. Significant differences in ELISA readings between the PATIN (65.49 %) and the AVERIN (15.97 %), LATIN (2.11 %), and LOWIN (3.27 %) groups were observed. In addition, significant differences in Map DNA copies/gram of feces were observed between the PATIN and the other three risk groups. These results together with the substantial economic impact of PTB in dairy cattle support the selection of the animals with less susceptibility to PTB in the Spanish breeding program.

ACS Style

Maria Canive; Rosa Casais; Jose A. Jimenez; Cristina Blanco-Vazquez; Javier Amado; Joseba M. Garrido; Ramon A. Juste; Marta Alonso-Hearn. Correlations between single nucleotide polymorphisms in bovine CD209, SLC11A1, SP110 and TLR2 genes and estimated breeding values for several traits in Spanish Holstein cattle. Heliyon 2020, 6, e04254 .

AMA Style

Maria Canive, Rosa Casais, Jose A. Jimenez, Cristina Blanco-Vazquez, Javier Amado, Joseba M. Garrido, Ramon A. Juste, Marta Alonso-Hearn. Correlations between single nucleotide polymorphisms in bovine CD209, SLC11A1, SP110 and TLR2 genes and estimated breeding values for several traits in Spanish Holstein cattle. Heliyon. 2020; 6 (6):e04254.

Chicago/Turabian Style

Maria Canive; Rosa Casais; Jose A. Jimenez; Cristina Blanco-Vazquez; Javier Amado; Joseba M. Garrido; Ramon A. Juste; Marta Alonso-Hearn. 2020. "Correlations between single nucleotide polymorphisms in bovine CD209, SLC11A1, SP110 and TLR2 genes and estimated breeding values for several traits in Spanish Holstein cattle." Heliyon 6, no. 6: e04254.

Journal article
Published: 16 October 2019 in Scientific Reports
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Paratuberculosis is chronic granulomatous enteritis of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Whole RNA-sequencing (RNA-Seq) is a promising source of novel biomarkers for early MAP infection and disease progression in cattle. Since the blood transcriptome is widely used as a source of biomarkers, we analyzed whether it recapitulates, at least in part, the transcriptome of the ileocecal valve (ICV), the primary site of MAP colonization. Total RNA was prepared from peripheral blood (PB) and ICV samples, and RNA-Seq was used to compare gene expression between animals with focal or diffuse histopathological lesions in gut tissues versus control animals with no detectable signs of infection. Our results demonstrated both shared, and PB and ICV-specific gene expression in response to a natural MAP infection. As expected, the number of differentially expressed (DE) genes was larger in the ICV than in the PB samples. Among the DE genes in the PB and ICV samples, there were some common genes irrespective of the type of lesion including the C-X-C motif chemokine ligand 8 (CXCL8/IL8), apolipoprotein L (APOLD1), and the interferon inducible protein 27 (IFI27). The biological processes (BP) enriched in the PB gene expression profiles from the cows with diffuse lesions included the killing of cells of other organism, defense response, immune response and the regulation of neutrophil chemotaxis. Two of these BP, the defense and immune response, were also enriched in the ICV from the cows with diffuse lesions. Metabolic analysis of the DE genes revealed that the N-glycan biosynthesis, bile secretion, one-carbon pool by folate and purine metabolism were significantly enriched in the ICV from the cows with focal lesions. In the ICV from cows with diffuse lesions; the valine, leucine and isoleucine degradation route, purine metabolism, vitamin digestion and absorption and the cholesterol routes were enriched. Some of the identified DE genes, BP and metabolic pathways will be studied further to develop novel diagnostic tools, vaccines and immunotherapeutics.

ACS Style

Marta Alonso-Hearn; Maria Canive; Cristina Blanco-Vazquez; Rosana Torremocha; Ana Balseiro; Javier Amado; Endika Varela; Ricardo Ramos; Begoña M. Jugo; Rosa Casais. RNA-Seq analysis of ileocecal valve and peripheral blood from Holstein cattle infected with Mycobacterium avium subsp. paratuberculosis revealed dysregulation of the CXCL8/IL8 signaling pathway. Scientific Reports 2019, 9, 14845 -17.

AMA Style

Marta Alonso-Hearn, Maria Canive, Cristina Blanco-Vazquez, Rosana Torremocha, Ana Balseiro, Javier Amado, Endika Varela, Ricardo Ramos, Begoña M. Jugo, Rosa Casais. RNA-Seq analysis of ileocecal valve and peripheral blood from Holstein cattle infected with Mycobacterium avium subsp. paratuberculosis revealed dysregulation of the CXCL8/IL8 signaling pathway. Scientific Reports. 2019; 9 (1):14845-17.

Chicago/Turabian Style

Marta Alonso-Hearn; Maria Canive; Cristina Blanco-Vazquez; Rosana Torremocha; Ana Balseiro; Javier Amado; Endika Varela; Ricardo Ramos; Begoña M. Jugo; Rosa Casais. 2019. "RNA-Seq analysis of ileocecal valve and peripheral blood from Holstein cattle infected with Mycobacterium avium subsp. paratuberculosis revealed dysregulation of the CXCL8/IL8 signaling pathway." Scientific Reports 9, no. 1: 14845-17.

Journal article
Published: 19 February 2019 in Journal of Theoretical Biology
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Understanding why pathogenic Mycobacterium avium subsp. paratuberculosis (Map) isolates cause disparate disease outcomes with differing magnitudes of severity is important in designing and implementing new control strategies. We applied a suite of mathematical models: i) general linear, ii) and neurofuzzy logic, to explain how the host of origin of several Map isolates, Map genotype, host, macrophage-based in vitro model and time post-infection contributed to the infection. A logistic growth ordinary differential equation (ODE) model was applied to estimate within macrophage growth rates for the different Map isolates. The models revealed different susceptibilities of bovine and ovine macrophages to Map infection and confirmed distinct virulence profiles for the isolates, judged by their ability to grow within macrophages. Ovine macrophages were able to internalized Map isolates more efficiently than bovine macrophages. While bovine macrophages were able to internalize Map isolates from cattle with more efficiency, ovine macrophages were more efficient in internalizing ovine isolates. Overall, Map isolates from goat and sheep grew minimally within macrophages or did not grow but were able to persist by maintaining its initial population. In contrast, the ability of the bovine isolates and the non-domesticated animal isolates to grow with higher CFU numbers within macrophages suggests that these isolates are more virulent than the sheep and goat isolates, or that these isolates are better adapted to infect domestic ruminants. Overall, our study confirms the different virulence levels for the Map isolates and susceptibility profiles of host macrophages, which is crucial in increasing our understanding of Map infection.

ACS Style

Marta Alonso-Hearn; Gesham Magombedze; Naiara Abendaño; Mariana Landin; Ramon A. Juste. Deciphering the virulence of Mycobacterium avium subsp. paratuberculosis isolates in animal macrophages using mathematical models. Journal of Theoretical Biology 2019, 468, 82 -91.

AMA Style

Marta Alonso-Hearn, Gesham Magombedze, Naiara Abendaño, Mariana Landin, Ramon A. Juste. Deciphering the virulence of Mycobacterium avium subsp. paratuberculosis isolates in animal macrophages using mathematical models. Journal of Theoretical Biology. 2019; 468 ():82-91.

Chicago/Turabian Style

Marta Alonso-Hearn; Gesham Magombedze; Naiara Abendaño; Mariana Landin; Ramon A. Juste. 2019. "Deciphering the virulence of Mycobacterium avium subsp. paratuberculosis isolates in animal macrophages using mathematical models." Journal of Theoretical Biology 468, no. : 82-91.

Original research article
Published: 21 March 2017 in Frontiers in Cellular and Infection Microbiology
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Johne´s disease is a chronic granulomatous enteritis of ruminants caused by the intracellular bacterium Mycobacterium avium subsp. paratuberculosis (Map). We previously demonstrated that Map isolates from sheep persisted within host macrophages in lower CFUs than cattle isolates after 7 days of infection. In the current study, we hypothesize that these phenotypic differences between Map isolates may be driven be the fatty acids (FAs) present on the phosphadidyl-1-myo-inositol mannosides of the Map cell wall that mediate recognition by the mannose receptors of host macrophages. FAs modifications may influence Map´s envelope fluidity ultimately affecting pathogenicity. To test this hypothesis, we investigated the responses of two Map isolates from cattle (K10 isolate) and sheep (2349/06-1) to the bovine and ovine macrophage environment by measuring the FAs content of extracellular and intracellular bacteria. For this purpose, macrophages cell lines of bovine (BOMAC) and ovine (MOCL-4) origin were infected with the two isolates of Map for 4 days at 37 °C. The relative FAs composition of the two isolates recovered from infected BOMAC and MOCL-4 cells was determined by gas chromatography and compared with that of extracellular bacteria and that of bacteria grown in Middlebrook 7H9 medium. Using this approach, we demonstrated that the FAs composition of extracellular and 7H9-grown bacteria was highly conserved within each Map isolate, and statistically different from that of intracellular bacteria. Analysis of FAs composition from extracellular bacteria enabled the distinction of the two Map strains based on the presence of the tuberculostearic acid (18:0 10Me) exclusively in the K10 strain of Map. In addition, significant differences in the content of Palmitic acid and cis-7 Palmitoleic acid between both isolates harvested from the extracellular environment were observed. Once the infection established itself in BOMAC and MOCL-4 cells, the FAs profiles of both Map isolates appeared relatively conserved. Our results suggest that the FAs composition of Map might influence its recognition by macrophages and influence the survival of the bacillus within host macrophages.

ACS Style

Marta Alonso-Hearn; Naiara Abendaño; Maria A. Ruvira; Rosa Aznar; Mariana Landin; Ramon A. Juste. Mycobacterium avium subsp. paratuberculosis (Map) Fatty Acids Profile Is Strain-Dependent and Changes Upon Host Macrophages Infection. Frontiers in Cellular and Infection Microbiology 2017, 7, 89 .

AMA Style

Marta Alonso-Hearn, Naiara Abendaño, Maria A. Ruvira, Rosa Aznar, Mariana Landin, Ramon A. Juste. Mycobacterium avium subsp. paratuberculosis (Map) Fatty Acids Profile Is Strain-Dependent and Changes Upon Host Macrophages Infection. Frontiers in Cellular and Infection Microbiology. 2017; 7 ():89.

Chicago/Turabian Style

Marta Alonso-Hearn; Naiara Abendaño; Maria A. Ruvira; Rosa Aznar; Mariana Landin; Ramon A. Juste. 2017. "Mycobacterium avium subsp. paratuberculosis (Map) Fatty Acids Profile Is Strain-Dependent and Changes Upon Host Macrophages Infection." Frontiers in Cellular and Infection Microbiology 7, no. : 89.

Journal article
Published: 14 October 2014 in Spanish Journal of Agricultural Research
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ACS Style

Patricia Vazquez; Joseba M. Garrido; Elena Molina; Maria V. Geijo; Nieves Gomez; Valentín Pérez; Iker A. Sevilla; Marta Alonso-Hearn; Adoracion Cortes; Ramón A. Juste. Latent infections are the most frequent form of paratuberculosis in slaughtered Friesian cattle. Spanish Journal of Agricultural Research 2014, 12, 1049 .

AMA Style

Patricia Vazquez, Joseba M. Garrido, Elena Molina, Maria V. Geijo, Nieves Gomez, Valentín Pérez, Iker A. Sevilla, Marta Alonso-Hearn, Adoracion Cortes, Ramón A. Juste. Latent infections are the most frequent form of paratuberculosis in slaughtered Friesian cattle. Spanish Journal of Agricultural Research. 2014; 12 (4):1049.

Chicago/Turabian Style

Patricia Vazquez; Joseba M. Garrido; Elena Molina; Maria V. Geijo; Nieves Gomez; Valentín Pérez; Iker A. Sevilla; Marta Alonso-Hearn; Adoracion Cortes; Ramón A. Juste. 2014. "Latent infections are the most frequent form of paratuberculosis in slaughtered Friesian cattle." Spanish Journal of Agricultural Research 12, no. 4: 1049.

Journal article
Published: 28 May 2014 in Clinical and Vaccine Immunology
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The enzyme-linked immunosorbent assay (ELISA) is the diagnostic test most commonly used in efforts to control paratuberculosis in domestic ruminants. However, commercial ELISAs have not been validated for detecting antibodies againstMycobacterium aviumsubsp.paratuberculosisin wild animals. In this study, we compared the sensitivities and specificities of five ELISAs using individual serum samples collected from 41 fallow deer with or without histopathological lesions consistent with paratuberculosis. Two target antigenic preparations were selected, an ethanol-treated protoplasmic preparation obtained from a fallow deerM. aviumsubsp.paratuberculosisisolate (ELISAs A and B) and a paratuberculosis protoplasmic antigen (PPA3) (ELISAs C and D). Fallow deer antibodies bound to the immobilized antigens were detected by using a horseradish peroxidase (HRP)-conjugated anti-fallow deer IgG antibody (ELISAs A and C) or HRP-conjugated protein G (ELISAs B and D). A commercially available assay, ELISA-E, which was designed to detectM. aviumsubsp.paratuberculosisantibodies in cattle, sheep, and goats, was also tested. Although ELISAs A, C, and E had the same sensitivity (72%), ELISAs A and C were more specific (100%) for detecting fallow deer with lesions consistent with paratuberculosis at necropsy than was the ELISA-E (87.5%). In addition, the ELISA-A was particularly sensitive for detecting fallow deer in the latent stages of infection (62.5%). The antibody responses detected with the ELISA-A correlated with both the severity of enteric lesions and the presence of acid-fast bacteria in gut tissue samples. In summary, our study shows that the ELISA-A can be a cost-effective diagnostic tool for preventing the spread of paratuberculosis among fallow deer populations.

ACS Style

José M. Prieto; Ana Balseiro; Rosa Casais; Naiara Abendaño; Liam E. Fitzgerald; Joseba M. Garrido; Ramon A. Juste; Marta Alonso-Hearn. Sensitive and Specific Enzyme-Linked Immunosorbent Assay for Detecting Serum Antibodies against Mycobacterium avium subsp. paratuberculosis in Fallow Deer. Clinical and Vaccine Immunology 2014, 21, 1077 -1085.

AMA Style

José M. Prieto, Ana Balseiro, Rosa Casais, Naiara Abendaño, Liam E. Fitzgerald, Joseba M. Garrido, Ramon A. Juste, Marta Alonso-Hearn. Sensitive and Specific Enzyme-Linked Immunosorbent Assay for Detecting Serum Antibodies against Mycobacterium avium subsp. paratuberculosis in Fallow Deer. Clinical and Vaccine Immunology. 2014; 21 (8):1077-1085.

Chicago/Turabian Style

José M. Prieto; Ana Balseiro; Rosa Casais; Naiara Abendaño; Liam E. Fitzgerald; Joseba M. Garrido; Ramon A. Juste; Marta Alonso-Hearn. 2014. "Sensitive and Specific Enzyme-Linked Immunosorbent Assay for Detecting Serum Antibodies against Mycobacterium avium subsp. paratuberculosis in Fallow Deer." Clinical and Vaccine Immunology 21, no. 8: 1077-1085.

Review article
Published: 21 May 2014 in BioMed Research International
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Mycobacterium tuberculosis,Mycobacterium leprae,Mycobacterium bovis,andMycobacterium aviumsubsp.paratuberculosiscan survive within host macrophages in a dormant state, encased within an organized aggregate of immune host cells called granuloma. Granulomas consist of uninfected macrophages, foamy macrophages, epithelioid cells, and T lymphocytes accumulated around infected macrophages. Within granulomas, activated macrophages can fuse to form multinucleated giant cells, also called giant Langhans cells. A rim of T lymphocytes surrounds the core, and a tight coat of fibroblast closes the structure. Severalin vivomodels have been used to study granuloma’s structure and function, but recently developedin vitromodels of granuloma show potential for closer observation of the early stages of host’s responses to live mycobacteria. This paper reviews culture conditions that resulted in three-dimensional granulomas, formed by the adhesion of cell populations in peripheral blood mononuclear cells infected with mycobacteria. The similarities of these models to granulomas encountered in clinical specimens include cellular composition, granulomas’ cytokine production, and cell surface antigens. A reliablein vitrodormancy model may serve as a useful platform to test whether drug candidates can kill dormant mycobacteria. Novel drugs that target dormancy-specific pathways may shorten the current long, difficult treatments necessary to cure mycobacterial diseases.

ACS Style

Liam E. Fitzgerald; Naiara Abendaño; Ramon Juste; Marta Alonso-Hearn. Three-DimensionalIn VitroModels of Granuloma to Study Bacteria-Host Interactions, Drug-Susceptibility, and Resuscitation of Dormant Mycobacteria. BioMed Research International 2014, 2014, 1 -8.

AMA Style

Liam E. Fitzgerald, Naiara Abendaño, Ramon Juste, Marta Alonso-Hearn. Three-DimensionalIn VitroModels of Granuloma to Study Bacteria-Host Interactions, Drug-Susceptibility, and Resuscitation of Dormant Mycobacteria. BioMed Research International. 2014; 2014 ():1-8.

Chicago/Turabian Style

Liam E. Fitzgerald; Naiara Abendaño; Ramon Juste; Marta Alonso-Hearn. 2014. "Three-DimensionalIn VitroModels of Granuloma to Study Bacteria-Host Interactions, Drug-Susceptibility, and Resuscitation of Dormant Mycobacteria." BioMed Research International 2014, no. : 1-8.

Journal article
Published: 01 May 2013 in Veterinary Microbiology
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Assessment of the virulence of isolates of Mycobacterium avium subsp. paratuberculosis (Map) exhibiting distinct genotypes and isolated from different hosts may help to clarify the degree to which clinical manifestations of the disease in cattle can be attributed to bacterial or to host factors. The objective of this study was to test the ability of 10 isolates of Map representing distinct genotypes and isolated from domestic (cattle, sheep, and goat), and wildlife animal species (fallow deer, deer, wild boar, and bison) to enter and grow in bovine macrophages. The isolates were previously typed using IS1311 PCR followed by restriction endonuclease analysis into types C, S or B. Intracellular growth of the isolates in a bovine macrophage-like cell line (BoMac) and in primary bovine monocyte-derived macrophages (MDM) was evaluated by quantification of CFU numbers in the initial inoculum and inside of the host cells at 2h and 7 d p.i. using an automatic liquid culture system (Bactec MGIT 960). Individual data illustrated that growth was less variable in BoMac than in MDM cells. All the isolates from goat and sheep hosts persisted within BoMac cells in lower CFU numbers than the other tested isolates after 7 days of infection regardless of genotype. In addition, BoMac cells exhibited differential inflammatory, apoptotic and destructive responses when infected with a bovine or an ovine isolate; which correlated with the differential survival of these strains within BoMac cells. Our results indicated that the survival of the tested Map isolates within bovine macrophages is associated with the specific host from which the isolates were initially isolated.

ACS Style

Naiara Abendaño; Iker A. Sevilla; José Miguel Prieto; Joseba M. Garrido; Ramon Juste; Marta Alonso-Hearn. Mycobacterium avium subspecies paratuberculosis isolates from sheep and goats show reduced persistence in bovine macrophages than cattle, bison, deer and wild boar strains regardless of genotype. Veterinary Microbiology 2013, 163, 325 -334.

AMA Style

Naiara Abendaño, Iker A. Sevilla, José Miguel Prieto, Joseba M. Garrido, Ramon Juste, Marta Alonso-Hearn. Mycobacterium avium subspecies paratuberculosis isolates from sheep and goats show reduced persistence in bovine macrophages than cattle, bison, deer and wild boar strains regardless of genotype. Veterinary Microbiology. 2013; 163 (3-4):325-334.

Chicago/Turabian Style

Naiara Abendaño; Iker A. Sevilla; José Miguel Prieto; Joseba M. Garrido; Ramon Juste; Marta Alonso-Hearn. 2013. "Mycobacterium avium subspecies paratuberculosis isolates from sheep and goats show reduced persistence in bovine macrophages than cattle, bison, deer and wild boar strains regardless of genotype." Veterinary Microbiology 163, no. 3-4: 325-334.

Review
Published: 01 February 2013 in Recent Patents on DNA & Gene Sequences
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This article reviews some of the recent patents on DNA vaccines against fish viruses, in particular against the novirhabdovirus infectious hematopoitic necrosis virus (IHNV). Although very effective in protecting fish against IHNV, only one DNA vaccine has been approved to date for use in Canada. In Europe and in US, its commercialization is restricted due to safety concerns.

ACS Style

Marta Alonso; Jo-Ann C. Leong. Licensed DNA Vaccines against Infectious Hematopoietic Necrosis Virus (IHNV). Recent Patents on DNA & Gene Sequences 2013, 7, 62 -65.

AMA Style

Marta Alonso, Jo-Ann C. Leong. Licensed DNA Vaccines against Infectious Hematopoietic Necrosis Virus (IHNV). Recent Patents on DNA & Gene Sequences. 2013; 7 (1):62-65.

Chicago/Turabian Style

Marta Alonso; Jo-Ann C. Leong. 2013. "Licensed DNA Vaccines against Infectious Hematopoietic Necrosis Virus (IHNV)." Recent Patents on DNA & Gene Sequences 7, no. 1: 62-65.

Review article
Published: 20 January 2013 in BioMed Research International
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Mycobacterium aviumsubsp.paratuberculosis(Map) is the causative agent of a chronic intestinal inflammation in ruminants named Johne's disease or paratuberculosis and a possible etiopathological agent of human Crohn's disease (CD). Analysis of macrophage transcriptomes in response toMapinfection is expected to provide key missing information in the understanding of the role of this pathogen in establishing an inappropriate and persistent infection in a susceptible host and of the molecular mechanisms that might underlie the early phases of CD. In this paper we summarize transcriptomic studies of human and bovine peripheral blood mononuclear cells (PBMC), monocyte-derived macrophages (MDMs), and macrophages-like cell linesin vitroinfected withMap. Most studies included in this paper consistently reported common gene expression signatures of bovine and human macrophages in response toMapsuch as enhanced expression of the anti-inflammatory cytokines IL-10 and IL-6, which promote bacterial survival. Overexpression of IL-10 could be responsible for theMap-associated reduction in the expression of the proapoptotic TNF-αgene observed in bovine and human macrophages.

ACS Style

Naiara Abendaño; Ramon Juste; Marta Alonso-Hearn. Anti-Inflammatory and Antiapoptotic Responses to Infection: A Common Denominator of Human and Bovine Macrophages Infected withMycobacterium aviumSubsp.paratuberculosis. BioMed Research International 2013, 2013, 1 -7.

AMA Style

Naiara Abendaño, Ramon Juste, Marta Alonso-Hearn. Anti-Inflammatory and Antiapoptotic Responses to Infection: A Common Denominator of Human and Bovine Macrophages Infected withMycobacterium aviumSubsp.paratuberculosis. BioMed Research International. 2013; 2013 ():1-7.

Chicago/Turabian Style

Naiara Abendaño; Ramon Juste; Marta Alonso-Hearn. 2013. "Anti-Inflammatory and Antiapoptotic Responses to Infection: A Common Denominator of Human and Bovine Macrophages Infected withMycobacterium aviumSubsp.paratuberculosis." BioMed Research International 2013, no. : 1-7.

Journal article
Published: 01 August 2012 in Journal of Clinical Microbiology
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Quantification of 11 clinical strains of Mycobacterium avium subsp. paratuberculosis isolated from domestic (cattle, sheep, and goat) and wildlife (fallow deer, deer, wild boar, and bison) animal species in an automatic liquid culture system (Bactec MGIT 960) was accomplished. The strains were previously isolated and typed using IS 1311 PCR followed by restriction endonuclease analysis (PCR-REA) into type C, S, or B. A strain-specific quantification curve was generated for each M. avium subsp. paratuberculosis strain by relating the time to detection in the liquid culture system to the estimated log 10 CFU in each inoculum. According to their growth curves, the tested M. avium subsp. paratuberculosis strains were classified into two distinct groups. The first group included the S-type strain isolated from goat and all the sheep strains with C, S, and B genotypes. A second group contained the C- and B-type strains isolated from cattle, goat, and wildlife animals with the exception of the fallow deer strain. The strains isolated from cattle or sheep showed similar strain-specific standard curves irrespective of their genotype. In contrast, the strains isolated from goat or from wildlife animal species varied in their rates of growth in liquid culture. Universal-standard curves and algorithms for the quantification of each group of strains were generated. In addition, the liquid culture system was compared with a real-time quantitative PCR system for the quantification of the 11 M. avium subsp. paratuberculosis strains. Correlations between the estimated log 10 CFU and M. avium subsp. paratuberculosis DNA copy numbers were very high for all the tested strains ( R ≥ 0.9).

ACS Style

Naiara Abendaño; Iker A. Sevilla; José M. Prieto; Joseba M. Garrido; Ramon Juste; Marta Alonso-Hearn. Quantification of Mycobacterium avium subsp. paratuberculosis Strains Representing Distinct Genotypes and Isolated from Domestic and Wildlife Animal Species by Use of an Automatic Liquid Culture System. Journal of Clinical Microbiology 2012, 50, 2609 -2617.

AMA Style

Naiara Abendaño, Iker A. Sevilla, José M. Prieto, Joseba M. Garrido, Ramon Juste, Marta Alonso-Hearn. Quantification of Mycobacterium avium subsp. paratuberculosis Strains Representing Distinct Genotypes and Isolated from Domestic and Wildlife Animal Species by Use of an Automatic Liquid Culture System. Journal of Clinical Microbiology. 2012; 50 (8):2609-2617.

Chicago/Turabian Style

Naiara Abendaño; Iker A. Sevilla; José M. Prieto; Joseba M. Garrido; Ramon Juste; Marta Alonso-Hearn. 2012. "Quantification of Mycobacterium avium subsp. paratuberculosis Strains Representing Distinct Genotypes and Isolated from Domestic and Wildlife Animal Species by Use of an Automatic Liquid Culture System." Journal of Clinical Microbiology 50, no. 8: 2609-2617.

Journal article
Published: 31 March 2011 in Fish & Shellfish Immunology
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We developed a suicidal DNA vaccine (pIRF1A-G-pMT-M) for salmonid fish susceptible to Infectious Hematopoietic Necrosis Virus (IHNV). The suicidal vaccine consists of two operons: i) an inducible fish promoter, the interferon regulatory factor 1A promoter (pIRF1A), driving the expression of the IHNV viral glycoprotein (G) gene that induces protection, and ii) a ZnCl(2) inducible fish promoter, the metallothionein promoter (pMT), driving the expression of the IHNV matrix (M) protein that induces apoptosis. The vaccine induces an immune response to the G protein and then induces the cell to undergo apoptosis to eliminate the DNA vaccine-containing cell. Also developed is another suicidal construct (pCMV-luc-pMT-M) for monitoring the persistence of luciferase (luc) expression after induction of apoptosis. In this study, we evaluated the inducibility of the MT promoter with ZnCl(2) and the capacity of cells transfected with the suicidal vector pCMV-luc-pMT-M to undergo apoptosis after ZnCl(2) addition. We also demonstrated the protective immunity elicited by the suicidal DNA vaccine pIRF1A-G-pMT-M, the survival of fish after treatment with ZnCl(2), and the elimination of the suicidal vector in fish after ZnCl(2) treatment.

ACS Style

Marta Alonso; Peter P. Chiou; Jo-Ann Leong. Development of a suicidal DNA vaccine for infectious hematopoietic necrosis virus (IHNV). Fish & Shellfish Immunology 2011, 30, 815 -823.

AMA Style

Marta Alonso, Peter P. Chiou, Jo-Ann Leong. Development of a suicidal DNA vaccine for infectious hematopoietic necrosis virus (IHNV). Fish & Shellfish Immunology. 2011; 30 (3):815-823.

Chicago/Turabian Style

Marta Alonso; Peter P. Chiou; Jo-Ann Leong. 2011. "Development of a suicidal DNA vaccine for infectious hematopoietic necrosis virus (IHNV)." Fish & Shellfish Immunology 30, no. 3: 815-823.

Journal article
Published: 01 May 2009 in Foodborne Pathogens and Disease
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Johne's disease or paratuberculosis is a chronic granulomatous inflammation of the small intestine of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Recent studies suggest an association between MAP and Crohn's disease in humans. MAP can become widely distributed within the tissues of infected animals, and meat may be a possible route of exposure of MAP to humans. In this study, 47 dairy and beef cattle were examined for the occurrence of viable MAP in diaphragm muscle. At the slaughterhouse, gut tissues, diaphragm muscle, blood, and feces of the 47 animals were collected for bacteriological culture, as well as gut samples for histopathological analysis. MAP was detected by bacteriological culture and conventional and real-time IS900 polymerase chain reaction in the diaphragm muscle of six infected cattle at slaughter (13%). The six animals showing evidence of MAP in diaphragm muscle had diffuse lesions and severe granulomatous inflammation in ileocecal lymph nodes, jejunal lymph nodes, ileocecal valve, and ileum. All six had heavy bacterial load in mesenteric lymph nodes, ileocecal valve, ileum, and jejunum, and four showed clinical signs of paratuberculosis. Two animals did not show clinical signs but had viable MAP in intestinal tissues and in diaphragm muscle as well. MAP was found in blood of only one of the six animals showing evidence of MAP in diaphragm muscle and in feces of three of them. In general, there was a positive association between enteric lesion severity, clinical signs of paratuberculosis, heavy bacterial load in intestinal tissues, fecal shedding of MAP, and the presence of disseminated MAP infection in diaphragm muscle. The results of this study demonstrated that MAP can be detected and cultured from muscle of MAP-infected cattle destined for human consumption and suggest a possible risk of exposure of humans to MAP via contaminated meat.

ACS Style

Marta Alonso-Hearn; Elena Molina; Mariví Geijo; Patricia Vazquez; Iker A. Sevilla; Joseba M. Garrido; Ramón A. Juste. Isolation ofMycobacterium aviumsubsp.paratuberculosisfrom Muscle Tissue of Naturally Infected Cattle. Foodborne Pathogens and Disease 2009, 6, 513 -518.

AMA Style

Marta Alonso-Hearn, Elena Molina, Mariví Geijo, Patricia Vazquez, Iker A. Sevilla, Joseba M. Garrido, Ramón A. Juste. Isolation ofMycobacterium aviumsubsp.paratuberculosisfrom Muscle Tissue of Naturally Infected Cattle. Foodborne Pathogens and Disease. 2009; 6 (4):513-518.

Chicago/Turabian Style

Marta Alonso-Hearn; Elena Molina; Mariví Geijo; Patricia Vazquez; Iker A. Sevilla; Joseba M. Garrido; Ramón A. Juste. 2009. "Isolation ofMycobacterium aviumsubsp.paratuberculosisfrom Muscle Tissue of Naturally Infected Cattle." Foodborne Pathogens and Disease 6, no. 4: 513-518.

Journal article
Published: 01 January 2009 in BMC Research Notes
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Paratuberculosis vaccination has been in use in some regions for many decades, but results have not been widely spread. A new Mycobacterium avium subsp. paratuberculosis (MAP) killed vaccine was studied in relationship with its effects on fecal shedding and milk production in four farms while other two were kept as controls submitted to a test and cull scheme.

ACS Style

Ramon A Juste; Marta Alonso-Hearn; Elena Molina; Mariví Geijo; Patricia Vazquez; Iker A. Sevilla; Joseba M Garrido. Significant reduction in bacterial shedding and improvement in milk production in dairy farms after the use of a new inactivated paratuberculosis vaccine in a field trial. BMC Research Notes 2009, 2, 233 -233.

AMA Style

Ramon A Juste, Marta Alonso-Hearn, Elena Molina, Mariví Geijo, Patricia Vazquez, Iker A. Sevilla, Joseba M Garrido. Significant reduction in bacterial shedding and improvement in milk production in dairy farms after the use of a new inactivated paratuberculosis vaccine in a field trial. BMC Research Notes. 2009; 2 (1):233-233.

Chicago/Turabian Style

Ramon A Juste; Marta Alonso-Hearn; Elena Molina; Mariví Geijo; Patricia Vazquez; Iker A. Sevilla; Joseba M Garrido. 2009. "Significant reduction in bacterial shedding and improvement in milk production in dairy farms after the use of a new inactivated paratuberculosis vaccine in a field trial." BMC Research Notes 2, no. 1: 233-233.

Journal article
Published: 13 December 2002 in Vaccine
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DNA plasmid vectors were constructed with inducible rainbow trout promoters to take the place of the cytomegalovirus immediate early promoter in DNA vaccines for fish. DNA fragments containing the promoter regions upstream of the rainbow trout Mx1 and interferon regulatory factor 1A (IRF1A) genes were obtained and their nucleotide sequences were determined. Vectors containing the G gene of IHNV linked to the trout promoters were found to be very effective as vaccines in rainbow trout. In addition, we demonstrated that the IRF1A promoter is transcriptionally active in mouse cells NIH-3T3 suggesting that this fish promoter might be used for mammalian DNA vaccine development as well.

ACS Style

Marta Alonso; Marc Johnson; Ben Simon; Jo-Ann Leong. A fish specific expression vector containing the interferon regulatory factor 1A (IRF1A) promoter for genetic immunization of fish. Vaccine 2002, 21, 1591 -1600.

AMA Style

Marta Alonso, Marc Johnson, Ben Simon, Jo-Ann Leong. A fish specific expression vector containing the interferon regulatory factor 1A (IRF1A) promoter for genetic immunization of fish. Vaccine. 2002; 21 (15):1591-1600.

Chicago/Turabian Style

Marta Alonso; Marc Johnson; Ben Simon; Jo-Ann Leong. 2002. "A fish specific expression vector containing the interferon regulatory factor 1A (IRF1A) promoter for genetic immunization of fish." Vaccine 21, no. 15: 1591-1600.

Journal article
Published: 01 January 2002 in Marine Biotechnology
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Previous attempts to identify genes in fish that respond to virus infection or interferon induction have not been particularly productive. Since these genes are very important in developing strategies to control disease outbreaks in aquaculture, we began a study of interferon-inducible genes in fish using suppressive subtraction hybridization to construct cDNA libraries enriched for interferon-inducible genes. Subtraction hybridization libraries were constructed with cDNA obtained from the kidney, spleen, and liver of Chinook salmon (Oncorhynchus tshawytscha) and staghorn sculpin (Hemilepidotus spinosus) before and after injection with poly IC, a potent interferon inducer. The "identified" genes in both cDNA libraries corresponded to previously identified genes of the fish complement system, the interferon-inducible proteins observed in mammalian cells, and the Vig-1 gene, identified in fish cells after infection with fish rhabdoviruses.

ACS Style

Marta Alonso; Jo-Ann Leong. Suppressive Subtraction Libraries to Identify Interferon-Inducible Genes in Fish. Marine Biotechnology 2002, 4, 0074 -0080.

AMA Style

Marta Alonso, Jo-Ann Leong. Suppressive Subtraction Libraries to Identify Interferon-Inducible Genes in Fish. Marine Biotechnology. 2002; 4 (1):0074-0080.

Chicago/Turabian Style

Marta Alonso; Jo-Ann Leong. 2002. "Suppressive Subtraction Libraries to Identify Interferon-Inducible Genes in Fish." Marine Biotechnology 4, no. 1: 0074-0080.