Back to Search
Start Over
Mycobacterium tuberculosis-infected alveolar epithelial cells modulate dendritic cell function through the HIF-1α-NOS2 axis.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2020 Oct; Vol. 108 (4), pp. 1225-1238. Date of Electronic Publication: 2020 Jun 18. - Publication Year :
- 2020
-
Abstract
- Tuberculosis kills more than 1 million people every year, and its control depends on the effective mechanisms of innate immunity, with or without induction of adaptive immune response. We investigated the interaction of type II alveolar epithelial cells (AEC-II) infected by Mycobacterium tuberculosis with dendritic cells (DCs). We hypothesized that the microenvironment generated by this interaction is critical for the early innate response against mycobacteria. We found that AEC-II infected by M. tuberculosis induced DC maturation, which was negatively regulated by HIF-1α-inducible NOS2 axis, and switched DC metabolism from an early and short peak of glycolysis to a low energetic status. However, the infection of DCs by M. tuberculosis up-regulated NOS2 expression and inhibited AEC-II-induced DC maturation. Our study demonstrated, for the first time, that HIF-1α-NOS2 axis plays a negative role in the maturation of DCs during M. tuberculosis infection. Such modulation might be useful for the exploitation of molecular targets to develop new therapeutic strategies against tuberculosis.<br /> (©2020 Society for Leukocyte Biology.)
- Subjects :
- Alveolar Epithelial Cells microbiology
Alveolar Epithelial Cells pathology
Animals
Dendritic Cells microbiology
Dendritic Cells pathology
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Mice
Mice, Knockout
Nitric Oxide Synthase Type II genetics
Tuberculosis, Pulmonary genetics
Tuberculosis, Pulmonary microbiology
Alveolar Epithelial Cells immunology
Dendritic Cells immunology
Hypoxia-Inducible Factor 1, alpha Subunit immunology
Mycobacterium tuberculosis immunology
Nitric Oxide Synthase Type II immunology
Tuberculosis, Pulmonary immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1938-3673
- Volume :
- 108
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 32557929
- Full Text :
- https://doi.org/10.1002/JLB.3MA0520-113R