The role of integrins in T cell-mediated resistance to Cryptosporidium parvum

Abstract

Cryptosporidium is a protozoan that infects epithelial cells of the small intestine and is a cause of diarrhea and death in immunocompromised individuals and malnourished children. Immunity to this parasite is mediated by an intestinal T cell response, which is generated in gut-associated lymphoid tissues and dependent on type 1 conventional dendritic cells (cDC1s). The initial priming of T cells is accompanied by changes in integrin expression and subsequent trafficking to the site of infection. The role of specific integrins in trafficking to the ileum during cryptosporidiosis is largely unknown. The development of a transgenic Cryptosporidium strain that expresses MHCI and MHCII-restricted model antigens provides the ability to track T cell responses to this parasite. Our studies in this system revealed marked changes in the integrin profile of parasite-specific T cells as they are activated and traffic to the gut, and demonstrate that cDC1s contribute to the expression of the integrins 4, {beta}7, {beta}1, and L. Surprisingly, blockade of the canonical gut-homing integrin 4{beta}7 does not impact the ability of parasite-specific T cells to access the gut. However, blockade of integrin L decreases the parasite-specific T cell frequency at the site of infection and delays control of parasite burden. These datasets highlight an 4{beta}7-independent mechanism of T cell trafficking to the small intestine and indicate that L is an integrin required for T cell-mediated resistance to Cryptosporidium.