title: Generation of Trypanosoma cruzi-specific CD8+ T-cell immunity is unaffected by the absence of type I interferon signaling.
abstract: Trypanosoma cruzi is a protozoan parasite that causes human Chagas' disease, a leading source of congestive heart failure in Central and South America. CD8+ T cells are critical for control of T. cruzi infection, and CD8+ T cells recognizing the immunodominant trans-sialidase gene-encoded peptide TSKB20 (ANYKFTLV) account for approximately 30% of the total CD8+ T-cell population at the peak of infection in C57BL/6 mice. Type I interferons (IFN-I) are pleiotropic cytokines that play a critical role in both innate and adaptive immunity against a variety of infections, but their induction and their role in infection are dictated by the infectious agent. Because type I IFNs and IFN-responsive genes are evident early after T. cruzi infection of host cells, we examined the influence of IFN-I on the development of CD8+ T-cell responses during this infection. Mice lacking the receptor for IFN-I (IFNARKO) and their wild-type counterparts both developed chronic infections and generated similar frequencies of immunodominant TSKB20- and subdominant TSKB18-specific CD8+ T cells following T. cruzi infection. In contrast, peak TSKB20-specific CD8+ T-cell responses generated during infection with vaccinia virus engineered to express TSKB20 were approximately 2.5-fold lower in IFNARKO mice than B6 mice, although after viral clearance, the frequencies of TSKB20-specific CD8+ T cells stabilized at similar levels. Together, these data suggest that IFN-I induction and biology are dependent upon the microbial context and emphasize the need to investigate various infection models for a full understanding of CD8+ T-cell development.
authors.affiliation: Department of Cellular Biology and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia 30502, USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Martin
authors.forename: Kaja
authors.initials: K
authors.lastname: Murali-Krishna
authors.forename: Rick L
authors.initials: RL
authors.lastname: Tarleton
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014355:Chagas Disease / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology / Q000502:physiology*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000502:physiology; D007370:Interferon Type I / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017471:Receptors, Interferon / Q000276:immunology / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D017471:Receptors, Interferon
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