Critical role of Valpha14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection.

Abstract

The present study was designed to elucidate the role of Valpha14(+) NKT cells in the host defense against pulmonary infection with Streptococcus pneumoniae using Jalpha281 gene-disrupted mice (Jalpha281KO 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 Valpha14(+) NKT cells, detected by an alpha-galactosylceramide (alpha-GalCer)-loaded CD1d tetramer, increased in thelung 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 phaseof infection in WT mice. In the lungs of Jalpha281KO 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-alpha synthesis in infected lungs was significantly reduced at 3 h and at both 3 and 6 h, respectively, in Jalpha281KO mice, compared to WT mice. In addition, treatment of mice with alpha-GalCer significantly improved the outcome of this infection. Our results demonstrated MCP-1-dependent recruitment of Valpha14(+) NKT cells and their critical role in early host protection against S. pneumoniae by promoting the trafficking of neutrophils to the site of infection.

• Authors: Kazuyoshi Kawakami, Natsuo Yamamoto, Yuki Kinjo, Kazuya Miyagi, Chikara Nakasone, Kaori Uezu, Takeshi Kinjo, Toshinori Nakayama, Masaru Taniguchi, Atsushi Saito
• Journal: European journal of immunology (Eur J Immunol) Vol. 33 Issue 12 Pg. 3322-30 (Dec 2003) ISSN: 0014-2980 [Print] Germany
• PMID: 14635040 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Differentiation, B-Lymphocyte
• Chemokine CCL2
• Chemokine CXCL2
• Chemokines
• Cxcl2 protein, mouse
• Galactosylceramides
• Histocompatibility Antigens Class II
• Receptors, Antigen, T-Cell, alpha-beta
• Tumor Necrosis Factor-alpha
• invariant chain

Topics

• Animals
• Antigens, Differentiation, B-Lymphocyte
• Chemokine CCL2 (physiology)
• Chemokine CXCL2
• Chemokines (biosynthesis)
• Galactosylceramides (pharmacology)
• Histocompatibility Antigens Class II
• Immunity, Innate
• Killer Cells, Natural (immunology)
• Lung (immunology)
• Mice
• Mice, Inbred C57BL
• Neutrophils (immunology)
• Pneumococcal Infections (immunology)
• Receptors, Antigen, T-Cell, alpha-beta (physiology)
• Tumor Necrosis Factor-alpha (biosynthesis)