TY - JOUR
T1 - CCL20/CCR6 blockade enhances immunity to RSV by impairing recruitment of DC
AU - Kallal, Lara E.
AU - Schaller, Matthew A.
AU - Lindell, Dennis M.
AU - Lira, Sergio A.
AU - Lukacs, Nicholas W.
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
KW - Chemokines
KW - DC
KW - Mucosal immunity
UR - http://www.scopus.com/inward/record.url?scp=77951087220&partnerID=8YFLogxK
U2 - 10.1002/eji.200939778
DO - 10.1002/eji.200939778
M3 - Article
C2 - 20101616
AN - SCOPUS:77951087220
SN - 0014-2980
VL - 40
SP - 1042
EP - 1052
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 4
ER -