IL-17A promotes intracellular growth of Mycobacterium by inhibiting apoptosis of infected macrophages

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Cruz, A (Author) Other; Ludovico, P (Author) Other; Torrado, E (Author) Other; Gama, JB (Author) Other; Sousa, J (Author) Other; Gaifem, J (Author) Other; Appelberg, R (Author) ICBAS; Rodrigues, F (Author) Other; Cooper, AM (Author) Other; Pedrosa, J (Author) Other; Saraiva, M (Author) Other; Castro, AG (Author) Other

Journal

Title: Frontiers In Immunology

Vol. 6

ISSN: 1664-3224

Publisher: Frontiers Media

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 1 Citation

Other information

Authenticus ID: P-00G-R7V

DOI: 10.3389/fimmu.2015.00498

Abstract (EN): The fate of infected macrophages is a critical aspect of immunity to mycobacteria. By depriving the pathogen of its intracellular niche, apoptotic death of the infected macrophage has been shown to be an important mechanism to control bacterial growth. Here, we show that IL-17 inhibits apoptosis of Mycobacterium bovis BCG- or Mycobacterium tuberculosis-infected macrophages thus hampering their ability to control bacterial growth. Mechanistically, we show that IL 17 inhibits p53, and impacts on the intrinsic apoptotic pathway, by increasing the BcI2 and decreasing Bax expression, decreasing cytochrome c release from the mitochondria, and inhibiting caspase-3 activation. The same effect of IL 17 was observed in infected macrophages upon blockade of p53 nuclear translocation. These results reveal a previously unappreciated role for the IL-17/p53 axis in the regulation of mycobacteria-induced apoptosis and can have important implications in a broad spectrum of diseases where apoptosis of the infected cell is an important host defense mechanism.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8