Differential ability of surface and endosomal TLRs to induce CD8 T cell responses in vivo

TLR activation on dendritic cells (DCs) induces DC maturation and secretion of proinflammatory cytokines, both of which are important for activation and differentiation of CD4 T cells. The importance of TLR activation on DCs for CD8 T cell responses is less clear. In this study, we tested the abilit...

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Veröffentlicht in:The Journal of immunology (1950) 2014-05, Vol.192 (9), p.4303-4315
Hauptverfasser: Mandraju, Rajakumar, Murray, Sean, Forman, James, Pasare, Chandrashekhar
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container_issue 9
container_start_page 4303
container_title The Journal of immunology (1950)
container_volume 192
creator Mandraju, Rajakumar
Murray, Sean
Forman, James
Pasare, Chandrashekhar
description TLR activation on dendritic cells (DCs) induces DC maturation and secretion of proinflammatory cytokines, both of which are important for activation and differentiation of CD4 T cells. The importance of TLR activation on DCs for CD8 T cell responses is less clear. In this study, we tested the ability of different TLRs to regulate CD8 T cell responses to pathogens. We found that although all TLRs are able to induce CD8 T cell activation in vitro, there are profound differences in their ability to activate CD8 T cells in vivo. The nucleic acid recognizing endosomal TLRs, TLR3 and TLR9, had a potent ability to induce CD8 T cell activation. However, the surface TLRs, TLR2 and TLR4, that recognize bacterial ligands were not only incapable of inducing CD8 T cell priming, but they had a dominant effect of inhibiting CD8 T cell expansion induced by activation of endosomal TLRs. We found that TLR2 and TLR4, acting in a MyD88-dependent manner, influenced CD8 T cell priming by altering the composition of DCs in the draining lymph nodes. Our results have important implications for combined bacterial and viral infections and suggest that bacterial infections could constrain the ability of the host to mount effective antiviral CD8 T cell immunity.
doi_str_mv 10.4049/jimmunol.1302244
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subjects Animals
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
Cell Differentiation - immunology
Cell Membrane - immunology
Cell Membrane - metabolism
Dendritic Cells - cytology
Dendritic Cells - immunology
Endosomes - immunology
Endosomes - metabolism
Flow Cytometry
Lymphocyte Activation - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Toll-Like Receptors - immunology
Toll-Like Receptors - metabolism
title Differential ability of surface and endosomal TLRs to induce CD8 T cell responses in vivo
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