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This Article Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901178v1 183/2/1245    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Padilla, A. M. Articles by Tarleton, R. L. PubMed PubMed Citation Articles by Padilla, A. M. Articles by Tarleton, R. L. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Chagas Disease

Insufficient TLR Activation Contributes to the Slow Development of CD8⁺ T Cell Responses in Trypanosoma cruzi Infection¹

Angel M. Padilla^*, Laura J. Simpson^* and Rick L. Tarleton^*,,2

*Center for Tropical and Emerging Global Diseases, Department of Cellular Biology, University of Georgia, Athens, GA 30602

During experimental infection with Trypanosoma cruzi, mice develop a strong CD8⁺ T cell response focused mainly on a few immunodominant peptides encoded in trans-sialidase family genes. Despite the potency of this response, the initial emergence and peak of parasite-specific CD8⁺ T cells has been noted to be relatively slow. In this study, we further document this delayed onset of T cell responses to T. cruzi as measured by the increase in frequency of parasite-specific T cells, the effector function of these cells, T cell proliferation in general, and the recruitment of cells into the draining lymph nodes. This delay does not appear to be the result of general immunosuppressive effects of the infection, a limitation in parasite numbers, or parasite trafficking to lymph nodes or to the specific epitope. Increasing the initial infecting dose or the density of parasite epitopes on APCs can modestly speed the generation of anti-T. cruzi T cell responses. Given these characteristics of the response, we propose that T. cruzi is a stealth invader, largely avoiding recognition by components of the innate immune system until the infection is well established. This conclusion is supported by the ability to accelerate the induction of T cell responses to T. cruzi by administration of ligands for TLR2 and TLR9 at the time of infection. These studies highlight a previously unappreciated mechanism of immune evasion, the surreptitious establishment of infection, by the protozoan T. cruzi.

² Address correspondence and reprint requests to Dr. Rick L. Tarleton, Center for Tropical and Emerging Global Diseases, Coverdell Center Room 310B, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602. E-mail address: tarleton{at}cb.uga.edu

¹ This work was supported by Grants R01 AI22070 and R01 AI33106 from the National Institutes of Health (to R.L.T.).