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Toll-like Receptors Induce a Phagocytic Gene Program through p38

Toll-like receptor (TLR) signaling and phagocytosis are hallmarks of macrophage-mediated innate immune responses to bacterial infection. However, the relationship between these two processes is not well established. Our data indicate that TLR ligands specifically promote bacterial phagocytosis, in b...

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Autores principales: Doyle, Sean E., O'Connell, Ryan M., Miranda, Gustavo A., Vaidya, Sagar A., Chow, Edward K., Liu, Philip T., Suzuki, Shinobu, Suzuki, Nobutaka, Modlin, Robert L., Yeh, Wen-Chen, Lane, Timothy F., Cheng, Genhong
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1887723/
https://www.ncbi.nlm.nih.gov/pubmed/14699082
http://dx.doi.org/10.1084/jem.20031237
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author Doyle, Sean E.
O'Connell, Ryan M.
Miranda, Gustavo A.
Vaidya, Sagar A.
Chow, Edward K.
Liu, Philip T.
Suzuki, Shinobu
Suzuki, Nobutaka
Modlin, Robert L.
Yeh, Wen-Chen
Lane, Timothy F.
Cheng, Genhong
author_facet Doyle, Sean E.
O'Connell, Ryan M.
Miranda, Gustavo A.
Vaidya, Sagar A.
Chow, Edward K.
Liu, Philip T.
Suzuki, Shinobu
Suzuki, Nobutaka
Modlin, Robert L.
Yeh, Wen-Chen
Lane, Timothy F.
Cheng, Genhong
author_sort Doyle, Sean E.
collection PubMed
description Toll-like receptor (TLR) signaling and phagocytosis are hallmarks of macrophage-mediated innate immune responses to bacterial infection. However, the relationship between these two processes is not well established. Our data indicate that TLR ligands specifically promote bacterial phagocytosis, in both murine and human cells, through induction of a phagocytic gene program. Importantly, TLR-induced phagocytosis of bacteria was found to be reliant on myeloid differentiation factor 88–dependent signaling through interleukin-1 receptor–associated kinase-4 and p38 leading to the up-regulation of scavenger receptors. Interestingly, individual TLRs promote phagocytosis to varying degrees with TLR9 being the strongest and TLR3 being the weakest inducer of this process. We also demonstrate that TLR ligands not only amplify the percentage of phagocytes uptaking Escherichia coli, but also increase the number of bacteria phagocytosed by individual macrophages. Taken together, our data describe an evolutionarily conserved mechanism by which TLRs can specifically promote phagocytic clearance of bacteria during infection.
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spelling pubmed-18877232008-03-11 Toll-like Receptors Induce a Phagocytic Gene Program through p38 Doyle, Sean E. O'Connell, Ryan M. Miranda, Gustavo A. Vaidya, Sagar A. Chow, Edward K. Liu, Philip T. Suzuki, Shinobu Suzuki, Nobutaka Modlin, Robert L. Yeh, Wen-Chen Lane, Timothy F. Cheng, Genhong J Exp Med Article Toll-like receptor (TLR) signaling and phagocytosis are hallmarks of macrophage-mediated innate immune responses to bacterial infection. However, the relationship between these two processes is not well established. Our data indicate that TLR ligands specifically promote bacterial phagocytosis, in both murine and human cells, through induction of a phagocytic gene program. Importantly, TLR-induced phagocytosis of bacteria was found to be reliant on myeloid differentiation factor 88–dependent signaling through interleukin-1 receptor–associated kinase-4 and p38 leading to the up-regulation of scavenger receptors. Interestingly, individual TLRs promote phagocytosis to varying degrees with TLR9 being the strongest and TLR3 being the weakest inducer of this process. We also demonstrate that TLR ligands not only amplify the percentage of phagocytes uptaking Escherichia coli, but also increase the number of bacteria phagocytosed by individual macrophages. Taken together, our data describe an evolutionarily conserved mechanism by which TLRs can specifically promote phagocytic clearance of bacteria during infection. The Rockefeller University Press 2004-01-05 /pmc/articles/PMC1887723/ /pubmed/14699082 http://dx.doi.org/10.1084/jem.20031237 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Doyle, Sean E.
O'Connell, Ryan M.
Miranda, Gustavo A.
Vaidya, Sagar A.
Chow, Edward K.
Liu, Philip T.
Suzuki, Shinobu
Suzuki, Nobutaka
Modlin, Robert L.
Yeh, Wen-Chen
Lane, Timothy F.
Cheng, Genhong
Toll-like Receptors Induce a Phagocytic Gene Program through p38
title Toll-like Receptors Induce a Phagocytic Gene Program through p38
title_full Toll-like Receptors Induce a Phagocytic Gene Program through p38
title_fullStr Toll-like Receptors Induce a Phagocytic Gene Program through p38
title_full_unstemmed Toll-like Receptors Induce a Phagocytic Gene Program through p38
title_short Toll-like Receptors Induce a Phagocytic Gene Program through p38
title_sort toll-like receptors induce a phagocytic gene program through p38
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1887723/
https://www.ncbi.nlm.nih.gov/pubmed/14699082
http://dx.doi.org/10.1084/jem.20031237
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