title: Type I interferons increase host susceptibility to Trypanosoma cruzi infection.
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.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Building I, Rm. 817, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Anne-Danielle C
authors.initials: AD
authors.lastname: Chessler
authors.forename: Kacey L
authors.initials: KL
authors.lastname: Caradonna
authors.forename: Akram
authors.initials: A
authors.lastname: Da'dara
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Burleigh
mesh_terms: D000818:Animals; D002469:Cell Separation; D014355:Chagas Disease / Q000276:immunology / Q000473:pathology; D004198:Disease Susceptibility / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D014349:Trypanosoma cruzi / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D016899:Interferon-beta