The present study was designed to elucidate the role of V § 14 + NKT cells in the host defense against pulmonary infection with Streptococcus pneumoniae using J § 281 gene-disrupted mice (J § 281KO mice) that lacked this lymphocyte subset. In these mice, pneumococcal infection was severely exacerbated, as shown by the shorter survival time and marked increase of live bacteria in the lung compared to wild-type (WT) mice. The proportion of V § 14 + NKT cells, detected by an § -galactosylceramide ( § -GalCer)-loaded CD1d tetramer, increased in the lung after S. pneumoniae infection. This increase was significantly reduced in mice with a genetic disruption of monocyte chemotactic protein (MCP)-1, which was produced in the early phase of infection in WT mice. In the lungs of J § 281KO mice, the number of neutrophils was significantly lower at 12 h than that in WT mice. In support of this finding, macrophage inflammatory protein (MIP)-2 and TNF- § synthesis in infected lungs was significantly reduced at 3 h and at both 3 and 6 h, respectively, in J § 281KO mice, compared to WT mice. In addition, treatment of mice with § -GalCer significantly improved the outcome of this infection. Our results demonstrated MCP-1-dependent recruitment of V § 14 + NKT cells and their critical role in early host protection against S. pneumoniae by promoting the trafficking of neutrophils to the site of infection.

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