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TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4(+) T Cells to T(reg)
CD4(+) T lymphocytes are crucial for controlling a range of innate and adaptive immune effectors. For CD8(+) cytotoxic T lymphocyte (CTL) responses, CD4(+) T cells can function as helpers (T(H)) to amplify magnitude and functionality or as regulatory cells (T(reg)) capable of profound inhibition. It...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903023/ https://www.ncbi.nlm.nih.gov/pubmed/32268093 http://dx.doi.org/10.1016/j.celrep.2020.01.040 |
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author | Dolina, Joseph S. Lee, Joey Griswold, Ryan Q. Labarta-Bajo, Lara Kannan, Sumetha Greenbaum, Jason A. El Idrissi, Nawal Bahia Pont, Margot J. Croft, Michael Schoenberger, Stephen P. |
author_facet | Dolina, Joseph S. Lee, Joey Griswold, Ryan Q. Labarta-Bajo, Lara Kannan, Sumetha Greenbaum, Jason A. El Idrissi, Nawal Bahia Pont, Margot J. Croft, Michael Schoenberger, Stephen P. |
author_sort | Dolina, Joseph S. |
collection | PubMed |
description | CD4(+) T lymphocytes are crucial for controlling a range of innate and adaptive immune effectors. For CD8(+) cytotoxic T lymphocyte (CTL) responses, CD4(+) T cells can function as helpers (T(H)) to amplify magnitude and functionality or as regulatory cells (T(reg)) capable of profound inhibition. It is unclear what determines differentiation to these phenotypes and whether pathogens provoke alternate programs. We find that, depending on the size of initial dose, Listeria infection drives CD4(+) T cells to act as T(H) or induces rapid polyclonal conversion to immunosuppressive T(reg). Conversion to T(reg) depends on the TLR9 and IL-12 pathways elicited by CD8a(+) dendritic cell (DC) sensing of danger-associated neutrophil self-DNA. These findings resolve long-standing questions regarding the conditional requirement for T(H) amongst pathogens and reveal a remarkable degree of plasticity in the function of CD4(+) T cells, which can be quickly converted to T(reg) in vivo by infection-mediated immune modulation. |
format | Online Article Text |
id | pubmed-8903023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-89030232022-03-08 TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4(+) T Cells to T(reg) Dolina, Joseph S. Lee, Joey Griswold, Ryan Q. Labarta-Bajo, Lara Kannan, Sumetha Greenbaum, Jason A. El Idrissi, Nawal Bahia Pont, Margot J. Croft, Michael Schoenberger, Stephen P. Cell Rep Article CD4(+) T lymphocytes are crucial for controlling a range of innate and adaptive immune effectors. For CD8(+) cytotoxic T lymphocyte (CTL) responses, CD4(+) T cells can function as helpers (T(H)) to amplify magnitude and functionality or as regulatory cells (T(reg)) capable of profound inhibition. It is unclear what determines differentiation to these phenotypes and whether pathogens provoke alternate programs. We find that, depending on the size of initial dose, Listeria infection drives CD4(+) T cells to act as T(H) or induces rapid polyclonal conversion to immunosuppressive T(reg). Conversion to T(reg) depends on the TLR9 and IL-12 pathways elicited by CD8a(+) dendritic cell (DC) sensing of danger-associated neutrophil self-DNA. These findings resolve long-standing questions regarding the conditional requirement for T(H) amongst pathogens and reveal a remarkable degree of plasticity in the function of CD4(+) T cells, which can be quickly converted to T(reg) in vivo by infection-mediated immune modulation. 2020-04-07 /pmc/articles/PMC8903023/ /pubmed/32268093 http://dx.doi.org/10.1016/j.celrep.2020.01.040 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Dolina, Joseph S. Lee, Joey Griswold, Ryan Q. Labarta-Bajo, Lara Kannan, Sumetha Greenbaum, Jason A. El Idrissi, Nawal Bahia Pont, Margot J. Croft, Michael Schoenberger, Stephen P. TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4(+) T Cells to T(reg) |
title | TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4(+) T Cells to T(reg) |
title_full | TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4(+) T Cells to T(reg) |
title_fullStr | TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4(+) T Cells to T(reg) |
title_full_unstemmed | TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4(+) T Cells to T(reg) |
title_short | TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4(+) T Cells to T(reg) |
title_sort | tlr9 sensing of self-dna controls cell-mediated immunity to listeria infection via rapid conversion of conventional cd4(+) t cells to t(reg) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903023/ https://www.ncbi.nlm.nih.gov/pubmed/32268093 http://dx.doi.org/10.1016/j.celrep.2020.01.040 |
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