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

Naoko Sato, Sunil K. Ahuja, Marion Quinones, Vannessa Kostecki, Robert L. Reddick, Peter C. Melby, William A. Kuziel, Seema S. Ahuja

Research output: Contribution to journalArticle

223 Scopus citations

Abstract

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 CCN5 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+ 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 cel - specific chemokine, may collectively contribute to the striking B cell outgrowth and Th2 cytokine - biased nonhealing phenotype that we observed in CCN2-deficient mice infected with L. major. This disease phenotype in mice with an L. major - resistant genetic background but lacking CCN2 is strikingly reminiscent of that observed typically in mice with an L. major - susceptible genetic background. Thus, CCN2 is an important determinant of not only DC migration and localization but also the development of protective cell-mediated immune responses to L. major.

Original languageEnglish (US)
Pages (from-to)205-218
Number of pages14
JournalJournal of Experimental Medicine
Volume192
Issue number2
DOIs
StatePublished - Jul 17 2000

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Keywords

  • Chemokine
  • Cytokine
  • Infectious immunity
  • Knockout
  • T helper cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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