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

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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 - 2008 Dec 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Saiga, H., Nishimura, J., Kuwata, H., Okuyama, M., Matsumoto, S., Sato, S., Matsumoto, M., Akira, S., Yoshikai, Y., Honda, K., Yamamoto, M., & Takeda, K. (2008). Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium. Journal of Immunology, 181(12), 8521-8527. https://doi.org/10.4049/jimmunol.181.12.8521