Cysteine-cysteinyl chemokine receptor 6 mediates invariant natural killer T cell airway recruitment and innate stage resistance during mycobacterial infection.
This study examined the contribution of cysteine-cysteinyl chemokine receptor 6 (CCR6) to the innate pulmonary antimycobacterial immune response. Using a mouse model of Mycobacterium bovis BCG airway infection, we detected maximal induction of the CCR6 agonist CCL20 in lungs at 1 week after infection. Infected CCR6 knockout (CCR6-/-) mice displayed an early impairment of bacterial clearance, but ultimately eliminated the attenuated organisms with the onset of adaptive immunity. Flow-cytometric analyses of bronchoalveolar lavages and dispersed lungs revealed a 60% reduction in TCR-α/β+ T cells in airways but no compromise of TCR-γ/δ+ T cells. The subset of CD1d-restricted, CD8-TCR-α/β+ natural killer cells, which mediate innate mycobacterial resistance, was profoundly reduced (90%). Analysis of the adaptive response using ovalbumin-specific transgenic TCR T cell (OT-II) transfer combined with infection with recombinant M. bovis BCG producing ovalbumin peptide indicated no impairment of adaptive T cell activation in CCR6-/- mice. There was also no impairment of the induction of cytokine-producing cells in draining lymphoid tissue of CCR6-/- mice. Taken together, our findings indicate that CCR6 is not required for induction of the adaptive antimycobacterial response, but is likely critical to airway compartment mobilization of TCR-α/β+CCR6+ innate and adaptive effector T cells.
Department of Pathology, University of Michigan Medical School Ann Arbor, Ann Arbor, Mich., USA.
Valerie R
VR
Stolberg
Bo-chin
BC
Chiu
Brian E
BE
Martin
Samir A
SA
Shah
Matyas
M
Sandor
Stephen W
SW
Chensue
D000818:Animals; D054418:Chemokine CCL20 / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology / Q000472:pathogenicity*; D055611:Natural Killer T-Cells / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D054399:Receptors, CCR6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology
C493447:CCL20 protein, mouse; C498126:CCR6 protein, mouse; D054418:Chemokine CCL20; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054399:Receptors, CCR6