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 |
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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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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. 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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.</description><subject>Animals</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Membrane - immunology</subject><subject>Cell Membrane - metabolism</subject><subject>Dendritic Cells - cytology</subject><subject>Dendritic Cells - immunology</subject><subject>Endosomes - immunology</subject><subject>Endosomes - metabolism</subject><subject>Flow Cytometry</subject><subject>Lymphocyte Activation - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Toll-Like Receptors - immunology</subject><subject>Toll-Like Receptors - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1LJDEQDeKyM-vu3ZPk6KW1kk4n6YsgM7oKA8Iylz2FTD40Q3dnTLoH_PdGHEVPBfVevapXD6FTAhcMWHu5DX0_DbG7IDVQytgRmpOmgYpz4MdoDqVZEcHFDP3KeQsAHCj7iWaUcSkLOEf_l8F7l9wwBt1hvQldGF9w9DhPyWvjsB4sdoONOfaFsF79y3iMOAx2KuBiKfEaG9d1OLm8i0N2uWB4H_bxN_rhdZfdn0M9Qevbm_Xirlo9_L1fXK8qU7d8rFgjpPUb1sraEA1SW6COilY64K5pmGw58dxYzQlYIWojtKHC1pI4u6G-PkFX77K7adM7a4qTpDu1S6HX6UVFHdR3ZAhP6jHuFSvfaaApAucHgRSfJ5dH1Yf8ZkkPLk5ZkYZIygSjpFDhnWpSzDk5_7mGgHoLRH0Eog6BlJGzr-d9DnwkUL8CbH2JpQ</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Mandraju, Rajakumar</creator><creator>Murray, Sean</creator><creator>Forman, James</creator><creator>Pasare, Chandrashekhar</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140501</creationdate><title>Differential ability of surface and endosomal TLRs to induce CD8 T cell responses in vivo</title><author>Mandraju, Rajakumar ; Murray, Sean ; Forman, James ; Pasare, Chandrashekhar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-4578dfb4983c1a08ad02e2798e06e5548961f6cda610d773c7ac27d381edb2f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>CD8-Positive T-Lymphocytes - cytology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell Differentiation - immunology</topic><topic>Cell Membrane - immunology</topic><topic>Cell Membrane - metabolism</topic><topic>Dendritic Cells - cytology</topic><topic>Dendritic Cells - immunology</topic><topic>Endosomes - immunology</topic><topic>Endosomes - metabolism</topic><topic>Flow Cytometry</topic><topic>Lymphocyte Activation - immunology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Toll-Like Receptors - immunology</topic><topic>Toll-Like Receptors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mandraju, Rajakumar</creatorcontrib><creatorcontrib>Murray, Sean</creatorcontrib><creatorcontrib>Forman, James</creatorcontrib><creatorcontrib>Pasare, Chandrashekhar</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mandraju, Rajakumar</au><au>Murray, Sean</au><au>Forman, James</au><au>Pasare, Chandrashekhar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential ability of surface and endosomal TLRs to induce CD8 T cell responses in vivo</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>192</volume><issue>9</issue><spage>4303</spage><epage>4315</epage><pages>4303-4315</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>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.</abstract><cop>United States</cop><pmid>24688022</pmid><doi>10.4049/jimmunol.1302244</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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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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