Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium

Hiroyuki Saiga, Junichi Nishimura, Hirotaka Kuwata, Megumi Okuyama, Sohkichi Matsumoto, Shintaro Sato, Makoto Matsumoto, Shizuo Akira, Yasunobu Yoshikai, Kenya Honda, Masahiro Yamamoto, Kiyoshi Takeda

    Research output: Contribution to journalArticle

    100 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)8521-8527
    Number of pages7
    JournalJournal of Immunology
    Volume181
    Issue number12
    DOIs
    Publication statusPublished - Dec 15 2008

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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