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Paradoxically high resistance of natural killer T (NKT) cell-deficient mice to Legionella pneumophila: another aspect of NKT cells for modulation of host responses

¹ Department of Microbiology and Infectious Diseases, Toho University, School of Medicine, Tokyo 143-8540, Japan

² Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

³ Department of Microbiology, Tokyo Medical University, Tokyo, Japan

⁴ Department of Pathology, Toho University School of Medicine, Tokyo, Japan

⁵ Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan

⁶ Laboratory of Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan

⁷ Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0360, USA

Correspondence
Kazuhiro Tateda
kazu{at}med.toho-u.ac.jp

Received November 4, 2007
Accepted August 1, 2008

In the present study, we examined the roles of natural killer T (NKT) cells in host defence against Legionella pneumophila in a mouse model. The survival rate of NKT cell-deficient J281 knock-out (KO) mice was significantly higher than that of wild-type mice. There was no bacterial overgrowth in the lungs, but J281 KO mice showed enhanced pulmonary clearance at a later stage of infection, compared with their wild-type counterparts. The severity of lung injury in L. pneumophila-infected J281 KO mice was less, as indicated by lung permeability measurements, such as lung weight and bronchoalveolar lavage fluid albumin concentration. Recruitment of inflammatory cells in the lungs was approximately twofold greater in J281 KO mice on day 3. Interestingly, higher values of interleukin (IL)-1β and IL-18, and increased caspase-1 activity were noted in the lungs of J281 KO mice from an early time point (6 h). Exogenous -galactosylceramide, a ligand of NKT cells, induced IL-12 and gamma interferon at 6 h, but suppressed IL-1β at later time points in wild-type, whereas no effects were evident in J281 KO mice, as expected. Systemic administration of heat-killed L. pneumophila, but not Escherichia coli LPS, reproduced exaggerated production of IL-1β in the lungs of J281 KO mice. These results demonstrate that NKT cells play a role in host defence against L. pneumophila, which is characterized by enhanced lung injury and decreased accumulation of inflammatory cells in the lungs. The regulation of IL-1β, IL-18 and caspase-1 may be associated with the modulating effect of host responses by NKT cells.

Abbreviations: BAL, bronchoalveolar lavage; -GalCer, -galactosylceramide; KO, knock-out; IFN-, gamma interferon; IL, interleukin; NK, natural killer; NKT, natural killer T.