Affiliation:
1. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Bldg. I, Rm. 810, 665 Huntington Ave., Boston, Massachusetts 02115
Abstract
ABSTRACT
Trypanosoma cruzi
, the protozoan parasite that causes human Chagas' disease, induces a type I interferon (IFN) (IFN-α/β) response during acute experimental infection in mice and in isolated primary cell types. To examine the potential impact of the type I IFN response in shaping outcomes in experimental
T. cruzi
infection, groups of wild-type (WT) and type I IFN receptor-deficient (IFNAR
−/−
) 129sv/ev mice were infected with two different
T. cruzi
strains under lethal and sublethal conditions and several parameters were measured during the acute stage of infection. The results demonstrate that type I IFNs are not required for early host protection against
T. cruzi
. In contrast, under conditions of lethal
T. cruzi
challenge, WT mice succumbed to infection whereas IFNAR
−/−
mice were ultimately able to control parasite growth and survive.
T. cruzi
clearance in and survival of IFNAR
−/−
mice were accompanied by higher levels of IFN-γ production by isolated splenocytes in response to parasite antigen. The suppression of IFN-γ in splenocytes from WT mice was independent of IL-10 levels. While the impact of type I IFNs on the production of IFN-γ and other cytokines/chemokines remains to be fully determined in the context of
T. cruzi
infection, our data suggest that, under conditions of high parasite burden, type I IFNs negatively impact IFN-γ production, initiating a detrimental cycle that contributes to the ultimate failure to control infection. These findings are consistent with a growing theme in the microbial pathogenesis field in which type I IFNs can be detrimental to the host in a variety of nonviral pathogen infection models.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
29 articles.
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