Caspase-8 Activity Prevents Type 2 Cytokine Responses and Is Required for Protective T Cell-Mediated Immunity against Trypanosoma cruzi Infection
| Autor: | Landi V. C. Guillermo, Renata M. Pereira, Richard M. Siegel, Marcela F. Lopes, Sérgio H. Seabra, Elisabeth M. Silva, Flávia L. Ribeiro-Gomes, Ulisses Gazos Lopes, Teresa Cristina Calegari-Silva, Zhengqi Wu, George A. DosReis, Juliana de Meis |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Trypanosoma cruzi CD3 medicine.medical_treatment T cell Immunology Mice Transgenic Biology T cell mediated immunity Mice Viral Proteins Interleukin 21 Th2 Cells medicine Animals Immunology and Allergy Cytotoxic T cell Chagas Disease Genetic Predisposition to Disease IL-2 receptor Cells Cultured Caspase 8 Immunity Cellular Mice Inbred BALB C Cell Differentiation Caspase Inhibitors Immunity Innate T cell cytokine production Up-Regulation Mice Inbred C57BL Cytokine medicine.anatomical_structure Caspases biology.protein Cytokines Oligopeptides |
| Zdroj: | The Journal of Immunology. 174:6314-6321 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.174.10.6314 |
| Popis: | During Trypanosoma cruzi infection, T cells up-regulate caspase-8 activity. To assess the role of caspase-8 in T cell-mediated immunity, we investigated the effects of caspase-8 inhibition on T cells in viral FLIP (v-FLIP) transgenic mice. Compared with wild-type controls, increased parasitemia was observed in v-FLIP mice infected with T. cruzi. There was a profound decrease in expansion of both CD4 and CD8 T cell subsets in the spleens of infected v-FLIP mice. We did not find differences in activation ratios of T cells from transgenic or wild-type infected mice. However, the numbers of memory/activated CD4 and CD8 T cells were markedly reduced in v-FLIP mice, possibly due to defective survival. We also found decreased production of IL-2 and increased secretion of type 2 cytokines, IL-4 and IL-10, which could enhance susceptibility to infection. Similar, but less pronounced, alterations were observed in mice treated with the caspase-8 inhibitor, zIETD. Furthermore, blockade of caspase-8 by zIETD in vitro mimicked the effects observed on T. cruzi infection in vivo, affecting the generation of activated/memory T cells and T cell cytokine production. Caspase-8 is also required for NF-κB signaling upon T cell activation. Blockade of caspase-8 by either v-FLIP expression or treatment with zIETD peptide decreased NF-κB responses to TCR:CD3 engagement in T cell cultures. These results suggest a critical role for caspase-8 in the establishment of T cell memory, cell signaling, and regulation of cytokine responses during protozoan infection. |
| Databáze: | OpenAIRE |
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