1. Mycobacterium tuberculosis-infected alveolar epithelial cells modulate dendritic cell function through the HIF-1α-NOS2 axis.
- Author
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Rodrigues TS, Alvarez ARP, Gembre AF, Forni MFPAD, de Melo BMS, Alves Filho JCF, Câmara NOS, and Bonato VLD
- 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
- 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., (©2020 Society for Leukocyte Biology.)
- Published
- 2020
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