Critical role of Vα14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection

Kazuyoshi Kawakami, Natsuo Yamamoto, Yuki Kinjo, Kazuya Miyagi, Chikara Nakasone, Kaori Uezu, Takeshi Kinjo, Toshinori Nakayama, Masaru Taniguchi, Atsushi Saito

Research output: Contribution to journalArticlepeer-review

152 Citations (Scopus)

Abstract

The present study was designed to elucidate the role of Vα14+ NKT cells in the host defense against pulmonary infection with Streptococcus pneumoniae using Jα281 gene-disrupted mice (Jα281KO 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 Vα14+ NKT cells, detected by an α-galactosylceramide (α-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 Jα281 KO 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-α synthesis in infected lungs was significantly reduced at 3 h and at both 3 and 6 h, respectively, in Jα281KO mice, compared to WT mice. In addition, treatment of mice with α-GalCer significantly improved the outcome of this infection. Our results demonstrated MCP-1-dependent recruitment of Vα14+ NKT cells and their critical role in early host protection against S. pneumoniae by promoting the trafficking of neutrophils to the site of infection.

Original languageEnglish
Pages (from-to)3322-3330
Number of pages9
JournalEuropean Journal of Immunology
Volume33
Issue number12
DOIs
Publication statusPublished - 2003 Dec
Externally publishedYes

Keywords

  • Host defense
  • Monocyte chemotactic protein-1
  • NKT cells
  • Neutrophils
  • Streptococcus pneumoniae

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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