Lipopolysaccharide or Whole Bacteria Block the Conversion of Inflammatory Monocytes into Dendritic Cells In Vivo

Monocytes can develop into dendritic cells (DCs) that migrate to lymph nodes (LNs) and present antigens to T cells. However, we find that this differentiation is blocked when monocytes accumulate subcutaneously in response to bacteria or lipopolysaccharide (LPS). The inhibition of DC differentiation...

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Main Authors: Rotta, Gianluca, Edwards, Emmerson W., Sangaletti, Sabina, Bennett, Clare, Ronzoni, Simona, Colombo, Mario P., Steinman, Ralph M., Randolph, Gwendalyn J., Rescigno, Maria
Format: Online
Language:English
Published: The Rockefeller University Press 2003
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194237/
id pubmed-2194237
recordtype oai_dc
spelling pubmed-21942372008-04-11 Lipopolysaccharide or Whole Bacteria Block the Conversion of Inflammatory Monocytes into Dendritic Cells In Vivo Rotta, Gianluca Edwards, Emmerson W. Sangaletti, Sabina Bennett, Clare Ronzoni, Simona Colombo, Mario P. Steinman, Ralph M. Randolph, Gwendalyn J. Rescigno, Maria Article Monocytes can develop into dendritic cells (DCs) that migrate to lymph nodes (LNs) and present antigens to T cells. However, we find that this differentiation is blocked when monocytes accumulate subcutaneously in response to bacteria or lipopolysaccharide (LPS). The inhibition of DC differentiation is mediated by the bacteria and in conjunction with inflammatory cells recruited at the site of injection. Inhibition of migratory DC development was reversed in Toll-like receptor (TLR)4-mutated mice when LPS, but not whole bacteria, was injected, suggesting that TLR4 is one but not the only mediator of the inhibition. The block imposed by bacteria was partly relieved by the absence of interleukin (IL)-12 p40, but not by individual absence of several cytokines involved in DC differentiation or in inflammation, i.e., IL-6, IL-10, IL-12 p35, and interferon γ. Consistent with the inability of monocytes to yield migrating DCs, and the finding that other DCs had limited access to particulate or bacterial antigens, these antigens were weakly presented to T cells in the draining LN. These results illustrate that bacteria-associated signals can have a negative regulatory role on adaptive immunity and that local innate responses for containment of infectious bacteria can at least initially supersede development of adaptive responses. The Rockefeller University Press 2003-10-20 /pmc/articles/PMC2194237/ /pubmed/14568983 http://dx.doi.org/10.1084/jem.20030335 Text en Copyright © 2003, 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/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Rotta, Gianluca
Edwards, Emmerson W.
Sangaletti, Sabina
Bennett, Clare
Ronzoni, Simona
Colombo, Mario P.
Steinman, Ralph M.
Randolph, Gwendalyn J.
Rescigno, Maria
spellingShingle Rotta, Gianluca
Edwards, Emmerson W.
Sangaletti, Sabina
Bennett, Clare
Ronzoni, Simona
Colombo, Mario P.
Steinman, Ralph M.
Randolph, Gwendalyn J.
Rescigno, Maria
Lipopolysaccharide or Whole Bacteria Block the Conversion of Inflammatory Monocytes into Dendritic Cells In Vivo
author_facet Rotta, Gianluca
Edwards, Emmerson W.
Sangaletti, Sabina
Bennett, Clare
Ronzoni, Simona
Colombo, Mario P.
Steinman, Ralph M.
Randolph, Gwendalyn J.
Rescigno, Maria
author_sort Rotta, Gianluca
title Lipopolysaccharide or Whole Bacteria Block the Conversion of Inflammatory Monocytes into Dendritic Cells In Vivo
title_short Lipopolysaccharide or Whole Bacteria Block the Conversion of Inflammatory Monocytes into Dendritic Cells In Vivo
title_full Lipopolysaccharide or Whole Bacteria Block the Conversion of Inflammatory Monocytes into Dendritic Cells In Vivo
title_fullStr Lipopolysaccharide or Whole Bacteria Block the Conversion of Inflammatory Monocytes into Dendritic Cells In Vivo
title_full_unstemmed Lipopolysaccharide or Whole Bacteria Block the Conversion of Inflammatory Monocytes into Dendritic Cells In Vivo
title_sort lipopolysaccharide or whole bacteria block the conversion of inflammatory monocytes into dendritic cells in vivo
description Monocytes can develop into dendritic cells (DCs) that migrate to lymph nodes (LNs) and present antigens to T cells. However, we find that this differentiation is blocked when monocytes accumulate subcutaneously in response to bacteria or lipopolysaccharide (LPS). The inhibition of DC differentiation is mediated by the bacteria and in conjunction with inflammatory cells recruited at the site of injection. Inhibition of migratory DC development was reversed in Toll-like receptor (TLR)4-mutated mice when LPS, but not whole bacteria, was injected, suggesting that TLR4 is one but not the only mediator of the inhibition. The block imposed by bacteria was partly relieved by the absence of interleukin (IL)-12 p40, but not by individual absence of several cytokines involved in DC differentiation or in inflammation, i.e., IL-6, IL-10, IL-12 p35, and interferon γ. Consistent with the inability of monocytes to yield migrating DCs, and the finding that other DCs had limited access to particulate or bacterial antigens, these antigens were weakly presented to T cells in the draining LN. These results illustrate that bacteria-associated signals can have a negative regulatory role on adaptive immunity and that local innate responses for containment of infectious bacteria can at least initially supersede development of adaptive responses.
publisher The Rockefeller University Press
publishDate 2003
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194237/
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