Growth hormone (GH) promotes body growth by binding with two GH receptors (GHRs) at the cell surface. GHRs interact with Janus kinase, signal transducers, and transcription activators to stimulate metabolic effects and insulin‐like growth factor (IGF) synthesis. However, process dysfunctions in the GH–GHR–IGF-1 axis cause animal dwarfism. If, during the GH process, GHR is not successfully recognized and/or bound, or GHR fails to transmit the GH signal to IGF-1, the GH dysfunction occurs. The goal of this review was to focus on the GHR mutations that lead to failures in the GH–GHR–IGF-1 signal transaction process in the dwarf phenotype. Until now, more than 90 GHR mutations relevant to human short stature (Laron syndrome and idiopathic short stature), including deletions, missense, nonsense, frameshift, and splice site mutations, and four GHR defects associated with chicken dwarfism, have been described. Among the 93 identified mutations of human GHR, 68 occur extracellularly, 13 occur in GHR introns, 10 occur intracellularly, and two occur in the transmembrane. These mutations interfere with the interaction between GH and GHRs, GHR dimerization, downstream signaling, and the expression of GHR. These mutations cause aberrant functioning in the GH-GHR-IGF-1 axis, resulting in defects in the number and diameter of muscle fibers as well as bone development.

SUMMARY Necrotic enteritis (NE) is an important enteric disease in poultry, and Clostridium perfringens (CP) type A strains are the primary etiology. NE is responsible for annual losses of US $6 billion to the poultry industry in the United States. An increase in the incidence of NE has been also associated with withdrawal of antibiotic growth promoters from poultry feed. In this study, CP strains isolated from healthy and NE-afflicted birds were characterized microbiologically and molecularly, and their virulence was experimentally tested in chickens. All strains were hemolytic, lecithinase positive, and identified as CP by biochemical tests. Three distinct colony morphologies were seen in brain-heart infusion media with 0.3% agarose, FeSO4, and ZnCl2. The CP strains responded differently to iron chelation with 2,2′-bidypinol. PCR toxinotyping showed that all tested strains were alpha toxin–positive, seven (N11, N10, CP1, CP5, CP13, JGS, and Del1) were beta2-toxin–positive, and only one (Del1) was necrot... RESUMEN Caracterización de las cepas de Clostridium perfringens aisladas de pollos de engorde sanos o con enteritis necrótica. La enteritis necrótica (NE) es una enfermedad entérica importante en la avicultura y las cepas de Clostridium perfringens (CP) tipo A son la etiología primaria. La enteritis necrótica es responsable de pérdidas anuales alrededor de seis mil millones de dólares para la industria avícola en los Estados Unidos. Un aumento en la incidencia de enteritis necrótica se ha asociado también con el retiro de los antibióticos utilizados como promotores del crecimiento de de los alimentos en avicultura. En este estudio, se caracterizaron microbiológicamente y molecularmente las cepas de C. perfringens aisladas de aves sanas y afectadas por enteritis necrótica y se analizó experimentalmente su virulencia en pollos. Todas las cepas fueron hemolíticas, lecitinasa positivas, e identificadas como C. perfringens por pruebas bioquímicas. Se observaron tres morfologías de colonias distintas en los med...

With the voluntary and regulatory withdrawal of antibiotic growth promoters from animal feed, coccidiosis and necrotic enteritis (NE) emerge as the top two enteric poultry infectious diseases responsible for major economic loss worldwide. The objective of this study was to investigate the correlation between the cecal microbiota compositions with the growth trait after coccidiosis and NE. In this study, the effects of Eimeria maxima and/or Clostridium perfringens infections on the microbial composition and potential correlation with the body weight gain were investigated in broiler chickens using 16S rRNA gene sequencing. E. maxima and C. perfringens coinfection successfully induced NE with its typical gut lesions and significant reductions in the percentage of relative body weight gain (RBWG%). The NE challenge model did not affect cecal microbial diversity, but influenced the cecal microbial composition. KEGG enzymes in microbiota were significantly altered in abundance following dual infections. Furthermore, significant correlations between cecal microbiota modules and RBWG% were identified in the sham control, E. maxima or C. perfringens infected groups. Understanding of host-microbiota interaction in NE would enhance the development of antibiotics-independent strategies to reduce the harmful effect of NE on the gut microbiota structure, and improve the gut health and poultry production.

Clostridium perfringens (CP) type A and newly created type G strains are the key etiological factors in the induction of necrotic enteritis (NE), an important enteric disease that is responsible for the annual loss of $6 billion in the worldwide poultry industry. Several CP toxin genes were found to be critical in NE pathogenesis in chickens, but limited information is available on the CP lethal toxin tpeL gene. In this study, 19 CP strains isolated from NE-affected chicken farms were characterized microbiologically and molecularly and evaluated for their pathogenicity in commercial broiler chickens. Toxin typing by PCR revealed that all strains tested were positive for the netB toxin gene, but only five strains were positive for the tpeL toxin gene (LLY-TpeL 13, -TpeL 15, -TpeL 17, -TpeL 18, and -TpeL 19, simplified as TpeL 13, TpeL 15, TpeL 17, TpeL 18, and TpeL 19). High levels of TpeL proteins were detected in the concentrated culture supernatant from strains TpeL 13, 15, 17, and 19 by western blotting. Quantitative PCR showed that strains TpeL 13, 15, 17, 18, and 19 harbored a high number of copies of tpeL genes, while TpeL 18 had the highest number of copies of the tpeL gene among all CP strains tested when normalized with copy numbers of 16S rRNA gene as a housekeeping gene marker. The in vivo NE challenge test using multiple oral CP inoculations combined with a high-protein diet showed that TpeL 17 was the most virulent in inducing typical NE lesions, followed by TpeL 19 as the next most virulent, when tested in commercial broiler chickens. Infection with TpeL 17 reduced the growth rate significantly, as shown by reduced relative body weight gain percentage at day 5 postinfection. Availability of the virulent netB+tpeL+ CP strains is essential for the development of a CP-alone NE challenge model that could provide significant tools for understanding CP pathogenesis and for development of alternative to antibiotics.

Haemonchus contortus has evolved highly integrated and sophisticated mechanisms to promote coexistence with hosts. The excretory-secretory (ES) products generated by this parasite contribute to the regulation of the host immune response to facilitate immune evasion and induce chronicity, but the proteins responsible for this process and the exact cellular mechanisms have yet to be defined. In this study, we identified 114 H. contortus ES proteins (HcESPs) interacting with host T cells and 15 T cell binding receptors via co-immunoprecipitation and shotgun liquid chromatography-tandem mass spectrometry analysis. Based on bioinformatics analysis, we demonstrated that HcESPs could inhibit T cell viability, induce cell apoptosis, suppress T cell proliferation and cause cell cycle arrest. Furthermore, the stimulation of HcESPs exerted critical control effects on T cell cytokine production profiles, predominantly promoting the secretion of interleukin (IL)-10, IL-17A and transforming growth factor-β1 and inhibiting IL-2, IL-4 and interferon-γ production. Collectively, these findings may provide insights into the interaction between ES proteins and key host effector cells, enhancing our understanding of the molecular mechanism underlying parasite immune evasion and providing new clues for novel vaccine development.

Apicomplexan protozoans of the genus Eimeria cause coccidiosis, one of the most economically relevant parasitic diseases in chickens. The lack of a complete understanding of molecular mechanisms in the host-parasite interaction limits the development of effective control measures. In the present study, RNA sequencing (RNA-Seq) was applied to investigate the host mRNA profiles of the cecal mucosa collected at day 5 post-infection with Eimeria maxima (EM). Total RNA from cecal samples of the uninfected naïve control and the EM groups was used to make libraries, generating 354,924,372 and 356,229,250 usable reads, respectively, which were assembled into a total of 386,088 high-quality unigenes (transcripts) in Trinity software. RNA-Seq analysis of cecal samples in the two groups revealed 332 upregulated and 363 downregulated genes with significant differences (P ≤ 0.05), including several significant immune-related gene families, such as the major histocompatibility complex (MHC) class I alpha chain, granzyme A and immunoglobulin subtype genes among upregulated differentially expressed genes. In addition, a total of 60 clusters of differentiation (CD) molecular genes and 570 novel genes were found. The completeness of the assembled transcriptome was further assessed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Gene ontology (GO), eggNOG and CAZy for gene annotation. The broad gene categories represented by the highly differentiated host genes suggested enrichment in immune responses, and downregulation in the metabolic pathway, MARK signaling pathway, vascular smooth muscle contraction, and proteins processing in endoplasmic reticulum after EM infection. Eimeria maxima induced statistically significant differences in the cecal mucosal gene expression of infected chickens. These findings provide new insights into the host-parasite interaction and enhance our understanding of the molecular mechanism of avian coccidiosis.