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 language | English |
|---|---|
| Pages (from-to) | 8521-8527 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 181 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 15 2008 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Immunology
Cite this
Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium. / Saiga, Hiroyuki; Nishimura, Junichi; Kuwata, Hirotaka; Okuyama, Megumi; Matsumoto, Sohkichi; Sato, Shintaro; Matsumoto, Makoto; Akira, Shizuo; Yoshikai, Yasunobu; Honda, Kenya; Yamamoto, Masahiro; Takeda, Kiyoshi.
In: Journal of Immunology, Vol. 181, No. 12, 15.12.2008, p. 8521-8527.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium
AU - Saiga, Hiroyuki
AU - Nishimura, Junichi
AU - Kuwata, Hirotaka
AU - Okuyama, Megumi
AU - Matsumoto, Sohkichi
AU - Sato, Shintaro
AU - Matsumoto, Makoto
AU - Akira, Shizuo
AU - Yoshikai, Yasunobu
AU - Honda, Kenya
AU - Yamamoto, Masahiro
AU - Takeda, Kiyoshi
PY - 2008/12/15
Y1 - 2008/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=58849133385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58849133385&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.181.12.8521
DO - 10.4049/jimmunol.181.12.8521
M3 - Article
C2 - 19050270
AN - SCOPUS:58849133385
VL - 181
SP - 8521
EP - 8527
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -