ena-STUDY-WASHINGTON UNIVERSITY SCHOOL OF MEDICINE-22-07-2021-03:30:57:453-430
Commensal Cryptosporidium colonization drives cDC1-dependent intestinal Th1 mediated homeostasis
Cryptosporidium is an important cause of infectious diarrhea; however, asymptomatic infections are not well characterized. Here, we studied the immunologic response to a commensal strain of Cryptosporidium tyzzeri (Ct-STL) serendipitously discovered when conventional type 1 dendritic cell (cDC1)-deficient mice developed fulminant cryptosporidiosis. We confirmed that Ct-STL behaved as a commensal in wild-type mice, as it was vertically transmitted with minimal deleterious health effects. Yet, Ct-STL provoked profound innate and adaptive changes in the intestinal immune system and induced a strong Ct-STL-specific Th1 cell response. cDC1s were critical for directing Th1 adaptive immunity, as cDC1-deficient mice skewed the Ct-STL response to Th17/Treg cell development. Although Ct-STL predominantly colonized the small intestine, colonic Th1 responses were also enhanced and were associated with protection against Citrobacter rodentium infection and exacerbation of dextran sodium sulfate/anti-IL10R colitis. Thus, Ct-STL represents a novel commensal pathobiont that elicits Th1-mediated homeostasis and exerts substantial effects on mucosal immunity of both the small and large intestine, and may reflect asymptomatic human Cryptosporidium infection.
Cryptosporidium is an important cause of infectious diarrhea; however, asymptomatic infections are not well characterized. Here, we studied the immunologic response to a commensal strain of Cryptosporidium tyzzeri (Ct-STL) serendipitously discovered when conventional type 1 dendritic cell (cDC1)-deficient mice developed fulminant cryptosporidiosis. We confirmed that Ct-STL behaved as a commensal in wild-type mice, as it was vertically transmitted with minimal deleterious health effects. Yet, Ct-STL provoked profound innate and adaptive changes in the intestinal immune system and induced a strong Ct-STL-specific Th1 cell response. cDC1s were critical for directing Th1 adaptive immunity, as cDC1-deficient mice skewed the Ct-STL response to Th17/Treg cell development. Although Ct-STL predominantly colonized the small intestine, colonic Th1 responses were also enhanced and were associated with protection against Citrobacter rodentium infection and exacerbation of dextran sodium sulfate/anti-IL10R colitis. Thus, Ct-STL represents a novel commensal pathobiont that elicits Th1-mediated homeostasis and exerts substantial effects on mucosal immunity of both the small and large intestine, and may reflect asymptomatic human Cryptosporidium infection.