Enhancement of IFNγ Production by Distinct Commensals Ameliorates Salmonella-Induced Disease

Abstract

The microbiota contributes to colonization resistance against invading pathogens by competing for metabolites, producing inhibitory substances, and priming protective immune responses. However, the specific commensal bacteria that promote host resistance and immune-mediated protection remain largely elusive. Using isogenic mouse lines with distinct microbiota profiles, we demonstrate that severity of disease induced by enteric Salmonella Typhimurium infection is strongly modulated by microbiota composition in individual lines. Transferring a restricted community of cultivable intestinal commensals from protected into susceptible mice decreases S. Typhimurium tissue colonization and consequently disease severity. This reduced tissue colonization, along with ameliorated weight loss and prolonged survival, depends on microbiota-enhanced IFNγ production, as IFNγ-deficient mice do not exhibit protective effects. Innate cells and CD4 T cells increase in number and show high levels of IFNγ after transfer of the commensal community. Thus, distinct microbiota members prevent intestinal Salmonella infection by enhancing antibacterial IFNγ responses.

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

“…However, IFN-γ deficiency does not exclude the activation of CD4 + T cells against this pathogen (83). Moreover, protective Th17 cells were induced against several intracellular pathogens, including Salmonella typhimurium (84) and L. m (85), indicating that Th17 cells are not redundant against intracellular pathogens. Thus, synergistically induced Th1 and Th17 cell responses will swiftly resolve the infection and limit tissue damage (86).…”

Colonization of preterm gnotobiotic piglets with probioticLactobacillus rhamnosusGG and its interference withSalmonellaTyphimurium

“…Local or systemic levels of IFN-γ were found in the term gnotobiotic [80,81] and conventional piglets [82] infected with Salmonella or other enteric bacterial pathogens. We measured local and systemic levels of IFN-γ to test if LGG shows an IFN-γ-stimulatory effect [79], but no levels of IFN-γ were found in the LGG group. Nevertheless, much more surprising was the absence of the stimulatory effect of Salmonella on IFN-γ levels in the intestine of both groups of the piglets infected with Salmonella (ST and LGG+ST) and the absence of IFN-γ levels (or their levels under the lower limit of detection) in blood.…”

Galactose-1-phosphate uridyltransferase (GalT), an in vivo-induced antigen of Actinobacillus pleuropneumoniae serovar 5b strain L20, provided immunoprotection against serovar 1 strain MS71

“…Clus-talX1.83 and MEGA5.05 were used to construct a phylogenetic tree of galT genes of the studied strains. The phylogenetic tree was set as 1, 000 bootstrap replicates and the Neighbor-Joining method was used [38].…”