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Cc Chemokine Receptor (Ccr)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-Inducing Dendritic Cells: Absence of Ccr2 Shifts the Leishmania major–Resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation
There is growing evidence that chemokines and their receptors regulate the movement and interaction of antigen-presenting cells such as dendritic cells (DCs) and T cells. We tested the hypothesis that the CC chemokine receptor (CCR)2 and CCR5 and the chemokine macrophage inflammatory protein (MIP)-1...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2000
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193245/ https://www.ncbi.nlm.nih.gov/pubmed/10899907 |
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author | Sato, Naoko Ahuja, Sunil K. Quinones, Marlon Kostecki, Vannessa Reddick, Robert L. Melby, Peter C. Kuziel, William A. Ahuja, Seema S. |
author_facet | Sato, Naoko Ahuja, Sunil K. Quinones, Marlon Kostecki, Vannessa Reddick, Robert L. Melby, Peter C. Kuziel, William A. Ahuja, Seema S. |
author_sort | Sato, Naoko |
collection | PubMed |
description | There is growing evidence that chemokines and their receptors regulate the movement and interaction of antigen-presenting cells such as dendritic cells (DCs) and T cells. We tested the hypothesis that the CC chemokine receptor (CCR)2 and CCR5 and the chemokine macrophage inflammatory protein (MIP)-1α, a ligand for CCR5, influence DC migration and localization. We found that deficiency of CCR2 but not CCR5 or MIP-1α led to distinct defects in DC biology. Langerhans cell (skin DC) density in CCR2-null mice was normal, and their ability to migrate into the dermis was intact; however, their migration to the draining lymph nodes was markedly impaired. CCR2-null mice had lower numbers of DCs in the spleen, and this was primarily due to a reduction in the CD8α(1) T helper cell type 1 (Th1)-inducing subset of DCs. Additionally, there was a block in the Leishmania major infection–induced relocalization of splenic DCs from the marginal zone to the T cell areas. We propose that these DC defects, in conjunction with increased expression of B lymphocyte chemoattractant, a B cell–specific chemokine, may collectively contribute to the striking B cell outgrowth and Th2 cytokine–biased nonhealing phenotype that we observed in CCR2-deficient mice infected with L. major. This disease phenotype in mice with an L. major–resistant genetic background but lacking CCR2 is strikingly reminiscent of that observed typically in mice with an L. major–susceptible genetic background. Thus, CCR2 is an important determinant of not only DC migration and localization but also the development of protective cell-mediated immune responses to L. major. |
format | Text |
id | pubmed-2193245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2000 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21932452008-04-16 Cc Chemokine Receptor (Ccr)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-Inducing Dendritic Cells: Absence of Ccr2 Shifts the Leishmania major–Resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation Sato, Naoko Ahuja, Sunil K. Quinones, Marlon Kostecki, Vannessa Reddick, Robert L. Melby, Peter C. Kuziel, William A. Ahuja, Seema S. J Exp Med Original Article There is growing evidence that chemokines and their receptors regulate the movement and interaction of antigen-presenting cells such as dendritic cells (DCs) and T cells. We tested the hypothesis that the CC chemokine receptor (CCR)2 and CCR5 and the chemokine macrophage inflammatory protein (MIP)-1α, a ligand for CCR5, influence DC migration and localization. We found that deficiency of CCR2 but not CCR5 or MIP-1α led to distinct defects in DC biology. Langerhans cell (skin DC) density in CCR2-null mice was normal, and their ability to migrate into the dermis was intact; however, their migration to the draining lymph nodes was markedly impaired. CCR2-null mice had lower numbers of DCs in the spleen, and this was primarily due to a reduction in the CD8α(1) T helper cell type 1 (Th1)-inducing subset of DCs. Additionally, there was a block in the Leishmania major infection–induced relocalization of splenic DCs from the marginal zone to the T cell areas. We propose that these DC defects, in conjunction with increased expression of B lymphocyte chemoattractant, a B cell–specific chemokine, may collectively contribute to the striking B cell outgrowth and Th2 cytokine–biased nonhealing phenotype that we observed in CCR2-deficient mice infected with L. major. This disease phenotype in mice with an L. major–resistant genetic background but lacking CCR2 is strikingly reminiscent of that observed typically in mice with an L. major–susceptible genetic background. Thus, CCR2 is an important determinant of not only DC migration and localization but also the development of protective cell-mediated immune responses to L. major. The Rockefeller University Press 2000-07-17 /pmc/articles/PMC2193245/ /pubmed/10899907 Text en © 2000 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 | Original Article Sato, Naoko Ahuja, Sunil K. Quinones, Marlon Kostecki, Vannessa Reddick, Robert L. Melby, Peter C. Kuziel, William A. Ahuja, Seema S. Cc Chemokine Receptor (Ccr)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-Inducing Dendritic Cells: Absence of Ccr2 Shifts the Leishmania major–Resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation |
title | Cc Chemokine Receptor (Ccr)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-Inducing Dendritic Cells: Absence of Ccr2 Shifts the Leishmania major–Resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation |
title_full | Cc Chemokine Receptor (Ccr)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-Inducing Dendritic Cells: Absence of Ccr2 Shifts the Leishmania major–Resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation |
title_fullStr | Cc Chemokine Receptor (Ccr)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-Inducing Dendritic Cells: Absence of Ccr2 Shifts the Leishmania major–Resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation |
title_full_unstemmed | Cc Chemokine Receptor (Ccr)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-Inducing Dendritic Cells: Absence of Ccr2 Shifts the Leishmania major–Resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation |
title_short | Cc Chemokine Receptor (Ccr)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-Inducing Dendritic Cells: Absence of Ccr2 Shifts the Leishmania major–Resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation |
title_sort | cc chemokine receptor (ccr)2 is required for langerhans cell migration and localization of t helper cell type 1 (th1)-inducing dendritic cells: absence of ccr2 shifts the leishmania major–resistant phenotype to a susceptible state dominated by th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193245/ https://www.ncbi.nlm.nih.gov/pubmed/10899907 |
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