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One of the major contributors to child mortality in the world is diarrheal diseases, with an estimated 800,000 deaths per year. Many pathogens are causative agents of these illnesses, including the enteropathogenic (EPEC) or enterohemorrhagic (EHEC) forms ofEscherichia coli. These bacteria are characterized by their ability to cause attaching and effacing lesions in the gut mucosa. Although much has been learned about the pathogenicity of these organisms and the immune response against them, the role of the intestinal microbiota during these infections is not well characterized. Infection of mice withE. colirequires pre-treatment with antibiotics in most mouse models, which hinders the study of the microbiota in an undisturbed environment. UsingCitrobacter rodentiumas a murine model for attaching and effacing bacteria, we show that C57BL/6 mice deficient in granzyme B expression are highly susceptible to severe disease caused byC. rodentiuminfection. Although a previous publication from our group shows that granzyme B-deficient CD4+T cells are partially responsible for this phenotype, in this report we present data demonstrating that the microbiota, in particular members of the order Turicibacterales, have an important role in conferring resistance. Mice deficient inTuricibacter sanguinishave increased susceptibility to severe disease. However, when these mice are co-housed with resistant mice, or colonized withT. sanguinis, susceptibility to severe infection is reduced. These results clearly suggest a critical role for this commensal in the protection against entero-pathogens. |
