Cysteine-Cysteinyl Chemokine Receptor 6 Mediates Invariant Natural Killer T Cell Airway Recruitment and Innate Stage Resistance during Mycobacterial Infection

• Published in: Journal of innate immunity 2011-01, Vol.3 (1), p.99-108
• Main Authors: Stolberg, Valerie R., Chiu, Bo-chin, Martin, Brian E., Shah, Samir A., Sandor, Matyas, Chensue, Stephen W.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell receptors; Cell structures and functions; Chemokine CCL20 - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects; Genetics of the immune response; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Humans; Immunity, Innate; Immunobiology; Lung - immunology; Lymphocyte Activation - immunology; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular and cellular biology; Mycobacterium bovis - immunology; Mycobacterium bovis - pathogenicity; Natural Killer T-Cells - immunology; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Receptors, CCR6 - genetics; Receptors, CCR6 - immunology; Receptors, CCR6 - metabolism; Research Article; T-Lymphocytes - immunology; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - microbiology
• ISSN: 1662-811X; 1662-8128
• DOI: 10.1159/000321156

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.