Bone marrow-derived circulating monocytes contribute to the replenishment and maintenance of the intestinal macrophage population. Intestinal monocytes undergo context-dependent phenotypic and functional adaptations to either maintain local immune balance or support intestinal inflammation. Here we use monocyte adoptive transfer to dissect the dynamics of monocyte-to-macrophage differentiation in normal and inflamed small intestine. We find that during homeostasis CCR2 and β7-integrin mediate constitutive homing of monocytes to the gut. By contrast, intestinal inflammation increases monocyte recruitment via CCR2, but not β7-integrin. In the non-inflamed intestine, monocytes gradually differentiate to express genes typically associated with tolerogenic macrophage functions. Conversely, immediately upon entry into the inflamed intestine, monocytes adapt a different expression pattern in a partly Trem-1-dependent manner. Our observations suggest that inflammation fundamentally changes the kinetics and modalities of monocyte differentiation in tissues.

M. tuberculosis and helminth infection each affects one third of the world population. Helminth infections down regulate cell mediated immune responses and this may contribute to lower efficacy of BCG vaccination and higher prevalence of tuberculosis. To determine the effect of maternal helminth infection on maternal and neonatal immune function and immunity to TB. In this cross sectional study, eighty five pregnant women were screened for parasitic and latent TB infections using Kato-Katz and QFT-GIT tests, respectively. IFN-γ and IL-4 ELISpot on Cord blood Mononuclear Cells, and total IgE and TB specific IgG ELISA on cord blood plasma was performed to investigate the possible effect of maternal helminth and/or latent TB co-infection on maternal and neonatal immune function and immunity to TB. The prevalence of helminth infections in pregnant women was 27% (n = 23), with Schistosoma mansoni the most common helminth species observed (20% of women were infected). Among the total of 85 study participants 25.8% were QFT-GIT positive and 17% had an indeterminate result. The mean total IgE value of cord blood was significantly higher in helminth positive than negative women (0.76 vs 0.47, p = 0.042). Cross placental transfer of TB specific IgG was significantly higher in helminth positive (21.9±7.9) than negative (12.3±5.1), p = 0.002) Latent TB Infection positive participants. The IFN-γ response of CBMCs to ESAT-6/CFP-10 cocktail (50 vs 116, p = 0.018) and PPD (58 vs 123, p = 0.02) was significantly lower in helminth positive than negative participants. There was no significant difference in IL-4 response of CBMCs between helminth negative and positive participants. Maternal helminth infection had a significant association with the IFN-γ response of CBMCs, total IgE and cross placental transfer of TB specific IgG. Therefore, further studies should be conducted to determine the effect of these factors on neonatal immune response to BCG vaccination.

Diarrhea caused by Shigella species results in long-term disability and mortality globally, disproportionally affecting younger children living in poor countries. Although it is treatable by antibiotics, the rapid and widespread emergence of resistant strains and the highly contagious nature of the disease compel the development of preventive tools.

Diarrhea caused by Shigella has been associated with high morbidity and mortality in young children worldwide. There are no licensed vaccines, and those clinically advanced have restricted coverage as they elicit serotype-specific immunity while disease is caused by multiple circulating serotypes. Our group had previously reported a close association between serum antibodies to the Shigella virulence factor VirG (or IcsA) and clinical protection in infected individuals. VirG is highly conserved among Shigella strains and appealing as a broad-spectrum vaccine candidate. In this study, we investigated the immunogenicity and protective capacity of VirG as a subunit vaccine in mice. The surface-exposed alpha (α) domain of VirG (VirGα) was produced as a recombinant protein. This region has almost identical immune reactivity to full-length VirG. Administered intramuscularly with alum, VirGα elicited robust immune responses and high protective efficacy against S. flexneri 2a and S. sonnei. Almost complete protection was afforded by VirGα given intranasally with the E. coli double mutant heat-labile toxin (dmLT). VirGα-specific antibodies recognized VirG expressed on live Shigella, and blocked Shigella adhesion and invasion to human colonic cells. These results show for the first time that VirGα is a promising cross-protective vaccine candidate to prevent Shigella infection.

To investigate the effect of pregnancy and Human immunodeficiency virus (HIV) infection on detection performances of tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFTGIT) for the diagnosis of latent tuberculosis infection (LTBI) among women living in high TB and HIV endemic setting. A cross-sectional study was conducted among women with and without pregnancy and HIV infection. Three-hundred twenty women were enrolled in this study and were diagnosed using TST and QFTGIT for the detection of LTBI. Overall prevalence of LTBI among the enrolled women was 55.6%, 46.3% and 51.1% as determined by TST, QFTGIT and concordant TST/QFTGIT results, respectively. Our study revealed that pregnancy or HIV infection reduced the rate of detection of LTBI by TST and QFTGIT tests, with the utmost effect observed in HIV-positive pregnant women. Additionally, we observed that the concordance between TST and QFTGIT among women increased with the presence of pregnancy and/or HIV infection. A history of contact with TB patients was significantly associated with positivity of TST and QFTGIT. This study demonstrated that both pregnancy and HIV infection profoundly affected the detection performance of TST and QFTGIT, which may be associated with immunosuppression of anti-mycobacterial immunity in women with pregnancy and/or HIV infection.

Background: Campylobacter species are the most predominant bacterial agents to cause diarrhea in under-five children. It poses a serious challenge to public health worldwide with ongoing acquisition of resistance to different antimicrobials with multiple patterns. Thus, this study aimed to determine the prevalence, and antimicrobial resistance of Campylobacter species, and associated factors among under-five children with diarrhea in selected public health facilities. Methods: A cross-sectional study was conducted among under-five children with diarrhea using convenient sampling. Health facilities were selected using a simple random sampling method. The stool samples collected from 214 study participants were transported and processed following standard microbiological protocols. Campylobacter isolates were identified using Gram staining, biochemical test, serological test, and aerobic growth at 25°C. Antimicrobial susceptibility profiles of isolates were performed using the Kirby–Bauer method. Data were analyzed using SPSS ver. 25.0. Association between variables was assessed using Chi-square test and Logistic regression, with P ≤ 0.05. Results: The subject’s mean age was 31.3 (± 3.9) months. Of the 214 samples cultured, 14 (6.5%) of them were positive for Campylobacter species with 95% CI (3.3– 10.3). Out of the isolated species, 12 (85.7%) were Campylobacter jejuni /Campylobacter coli and 2 (14.3%) were other Campylobacter species. Bottle feeding and history of direct contact to domestic animals were associated with Campylobacter species (AOR=5.13, CI=1.21– 21.6, p=0.026 and AOR=4.93, CI=1.33– 18.17, P=0.016), respectively. Campylobacter isolates were highly resistant to ciprofloxacin 5 (35.7%), and tetracycline 3 (21.4%). Conclusion: A higher incidence of Campylobacter species was obtained in children who were bottle-fed and who had a history of direct contact with domestic animals. The isolates were highly resistant to ciprofloxacin and tetracycline. These findings indicate that special attention is needed for better management of Campylobacter drug resistance in under-five children. To enhance and support our current findings, further research using molecular techniques is needed to identify the resistant and virulent genes of the bacterial isolates.