Respiratory tract Moraxella catarrhalisand Klebsiella pneumoniaecan promote pathogenicity of myelin-reactive Th17 cells

The respiratory tract is home to a diverse microbial community whose influence on local and systemic immune responses is only beginning to be appreciated. The airways have been linked with the trafficking of myelin-specific T cells in the preclinical stages of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. T helper (Th)17 cells are important pathogenic effectors in multiple sclerosis and EAE but are innocuous immediately following differentiation. Upregulation of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) appears to be a critical step in their acquisition of pathogenic potential, but little is known about the mechanisms that mediate this process. Here, primed myelin-specific Th17 cells were transferred to congenic recipient mice prior to exposure to various human respiratory tract-associated bacteria and T cell trafficking, and the phenotype and the severity of resulting EAE were monitored. The disease was exacerbated in mice exposed to the Proteobacteria Moraxella catarrhalisand Klebsiella pneumoniae,but not the Firmicute Veillonella parvula, and this was associated with a significant increase in GM-CSF+and GM-CSF+interferonγ+ex-Th17-like donor clusters of differentiation 4 T cells in the lungs and central nervous system of these mice. These findings support the concept that respiratory bacteria may contribute to the pathophysiology of central nervous system autoimmunity by modulating pathogenicity in crucial T-cell subsets that orchestrate neuroinflammation.