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The role of HIF-1a in the interaction of type II alveolar epithelial cells and dendritic cells during the immune response against Mycobacterium tuberculosis

Grant number: 17/16538-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): December 01, 2017
Effective date (End): January 31, 2019
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Vânia Luiza Deperon Bonato
Grantee:Tamara Silva Rodrigues
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Tuberculosis (TB) is a chronic infectious disease transmitted by the bacillus Mycobacterium tuberculosis (Mtb). Type II alveolar epithelial cells (AEC-II) are among the first cells to come into contact with Mtb. Mtb is able to replicate within AEC-II faster than in alveolar macrophages, making them reservoirs of the bacilli, which might help the infection development and the escape from the immune response. The AEC-II recognize Mtb constituents via standard recognition receptors (PRRs) and are activated, secreting cytokines, chemokines, antimicrobial peptides, and surfactant proteins. Thus, they might affect the microenvironment at the site of infection and regulate the response of immune cells close to them, such as dendritic cells (DCs). Metabolic reprogramming of phagocytes, associated with the response of proinflammatory cytokines and the production of microbicidal molecules are essential in controlling the growth of Mtb. An important transcription factor involved in this process is the hypoxia-induced factor (HIF-1a), which induces an increase of nitric oxide (NO) and IL-1b by macrophages infected with Mtb and leads to metabolic reprogramming for aerobic glycolysis in these cells. However, its function in AEC-II has not yet been fully elucidated. Therefore, our goal was to determine the role of HIF-1a in the interaction of Mtb infected AEC-II and DCs, regarding the activation and function of these cells. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
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. Mycobacterium tuberculosis-infected alveolar epithelial cells modulate dendritic cell function through the HIF-1 alpha-NOS2 axis. Journal of Leukocyte Biology, . (18/08479-7, 17/16538-0, 17/21629-5)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
RODRIGUES, Tamara Silva. Interaction of type II alveolar epithelial cells and dendritic cells in Mycobacterium tuberculosis infection: the role of HIF-1?. 2019. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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