Lipocalin 2-Dependent Inhibition of Mycobacterial Growth in Alveolar Epithelium
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- Hiroyuki Saiga
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka,
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- Junichi Nishimura
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka,
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- Hirotaka Kuwata
- Department of Molecular Genetics
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- Megumi Okuyama
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka,
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- Sohkichi Matsumoto
- Department of Bacteriology, Osaka City University Graduate School of Medicine , Osaka,
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- Shintaro Sato
- Department of Host Defense, Research Institute for Microbial Diseases
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- Makoto Matsumoto
- Department of Molecular Genetics
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- Shizuo Akira
- Department of Host Defense, Research Institute for Microbial Diseases
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- Yasunobu Yoshikai
- Division of Host Defense, Research Center for Prevention of Infectious Diseases, Medical Institute of Bioregulation, Kyushu University , Fukuoka,
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- Kenya Honda
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka,
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- Masahiro Yamamoto
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka,
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- Kiyoshi Takeda
- Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka,
書誌事項
- 公開日
- 2008-12
- 権利情報
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- https://academic.oup.com/pages/standard-publication-reuse-rights
- DOI
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- 10.4049/jimmunol.181.12.8521
- 公開者
- Oxford University Press (OUP)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>Mycobacterium tuberculosis invades alveolar epithelial cells as well as macrophages. However, the role of alveolar epithelial cells in the host defense against M. tuberculosis remains unknown. In this study, we report that lipocalin 2 (Lcn2)-dependent inhibition of mycobacterial growth within epithelial cells is required for anti-mycobacterial innate immune responses. Lcn2 is secreted into the alveolar space by alveolar macrophages and epithelial cells during the early phase of respiratory mycobacterial infection. Lcn2 inhibits the in vitro growth of mycobacteria through sequestration of iron uptake. Lcn2-deficient mice are highly susceptible to intratracheal infection with M. tuberculosis. Histological analyses at the early phase of mycobacterial infection in Lcn2-deficient mice reveal increased numbers of mycobacteria in epithelial cell layers, but not in macrophages, in the lungs. Increased intracellular mycobacterial growth is observed in alveolar epithelial cells, but not in alveolar macrophages, from Lcn2-deficient mice. The inhibitory action of Lcn2 is blocked by the addition of endocytosis inhibitors, suggesting that internalization of Lcn2 into the epithelial cells is a prerequisite for the inhibition of intracellular mycobacterial growth. Taken together, these findings highlight a pivotal role for alveolar epithelial cells during mycobacterial infection, in which Lcn2 mediates anti-mycobacterial innate immune responses within the epithelial cells.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 181 (12), 8521-8527, 2008-12
Oxford University Press (OUP)
