Mycobacterium tuberculosis-infected alveolar epithelial cells modulate dendritic cell function through the HIF-1 alpha-NOS2 axis

Author(s)

Rodrigues, Tamara Silva ; Alvarez, Annie Rocio Pineros ; Gembre, Ana Flavia ; Forni, Maria Fernanda Pereira de Araujo Demonte ; de Melo, Bruno Marcel Silva ; Alves Filho, Jose Carlos Farias ; Camara, Niels Olsen Saraiva ; Bonato, Vania Luiza Deperon

• Document type: Journal article
• Source: Journal of Leukocyte Biology; v. 108, n. 4, p. 14-pg., 2020-06-18.

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 byMycobacterium tuberculosiswith 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 byM. tuberculosisinduced DC maturation, which was negatively regulated by HIF-1 alpha-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 byM. tuberculosisup-regulated NOS2 expression and inhibited AEC-II-induced DC maturation. Our study demonstrated, for the first time, that HIF-1 alpha-NOS2 axis plays a negative role in the maturation of DCs duringM. tuberculosisinfection. Such modulation might be useful for the exploitation of molecular targets to develop new therapeutic strategies against tuberculosis. (AU)

• FAPESP's process: 17/21629-5 - Strategies to study pulmonary inflammation during comorbidities
• Grantee: Vânia Luiza Deperon Bonato
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/16538-0 - The role of HIF-1a in the interaction of type II alveolar epithelial cells and dendritic cells during the immune response against Mycobacterium tuberculosis
• Grantee: Tamara Silva Rodrigues
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/08479-7 - Multi-user equipment approved in grant 17/05264-7: analisador de fluxo extracelular Seahorse XFe96
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Multi-user Equipment Program