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Trypanosoma cruzi Triggers an Early Type I IFN Response In Vivo at the Site of Intradermal Infection¹

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston MA 02115

Early interactions between the protozoan parasite Trypanosoma cruzi and mammalian hosts at primary sites of infection (skin and mucosal membranes) are predicted to be critical determinants of parasite survival and dissemination in the host. To investigate the early host response triggered by three different strains of T. cruzi at a local infection site, changes in host gene expression were monitored in a murine intradermal infection model using Affymetrix oligonucleotide arrays. Robust induction of IFN-stimulated genes was observed in excised skin 24 h postinfection where the level of IFN-stimulated gene induction was parasite strain-dependent, with the least virulent strain triggering a muted IFN response. Infection of mice immunodepleted of IFN--producing cells or infection of IFN--deficient mice had minimal impact on the IFN response generated in T. cruzi-infected mice. In contrast, infection of mice lacking the type I IFN receptor demonstrated that type I IFNs are largely responsible for the IFN response generated at the site of infection. These data highlight type I IFNs as important components of the innate immune response to T. cruzi at the site of inoculation and their role in shaping the early transcriptional response to this pathogen.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant AI047960 and Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases (to B.A.B.).

² A.-D.C.C. and M.U. contributed equally to the studies presented in this paper.

³ Address correspondence and reprint requests to Dr. Barbara A. Burleigh, Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Building I, Room 817, Boston, MA 02115. E-mail address: bburleig{at}hsph.harvard.edu

⁴ Abbreviations used in this paper: i.d., intradermal; ISG, IFN-stimulated gene; FDR, false discovery rate; IFNAR, type I IFN receptor; MEF, mouse embryonic fibroblast; PMN, polymorphonuclear cell.

⁵ The online version of this article contains supplemental material.