CD8+ T cells maintain parasite control in nonlymphoid tissue during Trypanosoma cruzi infection
Collins, Matthew Harmon
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Trypanosoma cruzi establishes a persistent infection in mammalian hosts and causes Chagas disease in humans. CD8+ T cells are required for survival of acute infection by this parasite, but the role of these cells in chronic phase infection is not as well defined. It had been proposed that T cell dysfunction, a process observed in several chronic viral infections, could permit parasite persistence in nonlymphoid tissue. However, clearance of T. cruzi from skeletal muscle was not enhanced by blocking well described immunoregulatory mechanisms involving the inhibitory coreceptor PD-1 or IL-10. In contrast, this work shows that CD8+ T cells specific for T. cruzi-derived antigen are selectively activated in sites of parasite persistence, and depletion of CD8+ T cells during chronic phase infection results in loss of optimal parasite control. Because T. cruzi can be acquired via mucosal surfaces including the GI tract, the effect of oral infection on the CD8+ T cell response to T. cruzi was investigated. The data herein suggest that the route of infection does not alter the ability of T. cruzi to establish infection in muscle tissue. Also, mice generate a robust CD8+ T cell response to oral T. cruzi infection with a similar tissue distribution of T. cruzi-specific CD8+ T cells compared to foot pad infection. Finally, the vaccine efficacy of orally-administered attenuated parasites was tested. Orally immunized mice were protected from foot pad challenge infection with wild type T. cruzi, supporting development of whole-organism-based vaccines that target reservoir species as a means to alleviate the burden of Chagas disease in endemic areas.