CCL20/CCR6 blockade enhances immunity to RSV by impairing recruitment of DC

Lara E. Kallal, Matthew A. Schaller, Dennis M. Lindell, Sergio A. Lira, Nicholas W. Lukacs

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Chemokines are important mediators of the immune response to pathogens, but can also promote chronic inflammatory states. Chemokine receptor 6 (CCR6) is found on immature DC and effector/memory T cells, and binds a single ligand, CCL20, with high affinity. Here, we investigated the role of CCL20 and CCR6 in a pulmonary viral infection caused by RSV, a ubiquitous virus that can cause severe pulmonary complications. Neutralization of CCL20 during RSV infection significantly reduced lung pathology and favored a Th1 effector response. CCR6-deficient animals recapitulated this phenotype, and additionally showed enhanced viral clearance when compared with WT mice. No differences were observed in migration of T cells to the lungs of CCR6-/- animals; however, a significant reduction was observed in numbers of conventional DC (cDC), but not plasmacytoid DC, in CCR6-/- mice. A pathogenic phenotype could be reconstituted in CCR6-/- mice by supplying cDC into the airway, indicating that mere number of cDC dictates the adverse response. Our data suggest that blockade of the CCL20/CCR6 pathway provides an environment whereby the attenuated recruitment of cDC alters the balance of innate immune cells and mediates the efficient antiviral response to RSV.

Original languageEnglish
Pages (from-to)1042-1052
Number of pages11
JournalEuropean Journal of Immunology
Volume40
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

  • Chemokines
  • DC
  • Mucosal immunity

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