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Infection and Immunity, May 2005, p. 2709-2717, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2709-2717.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Legionella pneumophila Evades Gamma Interferon-Mediated Growth Suppression through Interleukin-10 Induction in Bone Marrow-Derived Macrophages

Sadako Yoshizawa,1 Kazuhiro Tateda,1* Tetsuya Matsumoto,1 Fumio Gondaira,2 Shuichi Miyazaki,1 Theodore J. Standiford,3 and Keizo Yamaguchi1

Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo 143-8540,1 Denkaseiken Co. Ltd., Gosenshi, Minami-Motomachi 1-2-2, Niigata 959-16, Japan,2 Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-03603

Received 20 August 2004/ Returned for modification 4 October 2004/ Accepted 6 January 2005

We examined the roles of Th1-Th2 cytokine cross talk in Legionella pneumophila-infected bone marrow-derived (BM) macrophages in the presence of costimulation with interleukin-12 (IL-12) and IL-18. Treatment with gamma interferon (IFN-{gamma}) alone or treatment with IL-12 in combination with IL-18 resulted in a 3- or 2-log reduction in bacterial numbers, respectively, in BM macrophages, whereas treatment with IL-12 or IL-18 alone had no effect. Significant amounts of IFN-{gamma} were detected in the culture supernatants of infected macrophages stimulated with IL-12 and IL-18 in combination but not independently. Neutralization of IFN-{gamma} by antibody completely abolished the growth inhibitory effects of IL-12 and IL-18. Interestingly, higher infectivity ratios of L. pneumophila or the addition of increasing concentrations of heat-killed bacteria (HKB) suppressed the production of IFN-{gamma}, which resulted in the increased intracellular growth of bacteria. Significant amounts of IL-10 were detected in culture supernatants when Legionella-infected macrophages were cocultured with HKB. Furthermore, neutralization of IL-10 by antibody resulted in an increase in IFN-{gamma} production by infected BM macrophages when cocultured with HKB. Treatment of HKB with trypsin but not polymyxin B attenuated the growth-promoting effects of HKB, suggesting the involvement of a protein component(s) in regulation of the growth of L. pneumophila. These findings demonstrate a crucial role of Th1-Th2 cross talk in L. pneumophila-infected BM macrophages. Our results also suggest that L. pneumophila modulates the cytokine balance from IFN-{gamma}-driven Th1 to more Th2 responses, likely through the induction of IL-10 by a bacterial protein component(s). These data provide new insights not only into the cellular mechanisms of Th1-Th2 cross talk in Legionella-infected macrophages but also into the pathogenesis of L. pneumophila pneumonia in humans.

* Corresponding author. Mailing address: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, 5-21-16 Ohmorinishi, Ohtaku, Tokyo 143-8540, Japan. Phone: 81-3-3762-4151, ext. 2396. Fax: 81-3-5493-5415. E-mail: kazu{at}med.toho-u.ac.jp.

Editor: J. L. Flynn

Infection and Immunity, May 2005, p. 2709-2717, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2709-2717.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Fuse, E. T., Tateda, K., Kikuchi, Y., Matsumoto, T., Gondaira, F., Azuma, A., Kudoh, S., Standiford, T. J., Yamaguchi, K. (2007). Role of Toll-like receptor 2 in recognition of Legionella pneumophila in a murine pneumonia model. J Med Microbiol 56: 305-312 [Abstract] [Full Text]  


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