Back to Search Start Over

IL-17A Promotes Intracellular Growth of Mycobacterium by Inhibiting Apoptosis of Infected Macrophages

Authors :
Andrea Cruz
Paula Ludovico
António G. Castro
Jorge Pedrosa
Egídio Torrado
Andrea M. Cooper
Jeremy Sousa
Rui Appelberg
Fernando Rodrigues
José B. Gama
Margarida Saraiva
Joana Gaifem
Universidade do Minho
Source :
Frontiers in Immunology, Vol 6 (2015), Frontiers in Immunology, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP
Publication Year :
2015
Publisher :
Frontiers Media SA, 2015.

Abstract

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 Bcl2 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.<br />Fundação para a Ciência e Tecnologia, Portugal. Project grants: PTDC/SAU-MII/101977/2008 (to AGC), PTDC/BIA-BCM/102776/2008 (to MS) and HMSP-ICT/0024/2010 (to RA) and co-funded by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), through the Fundo Europeu de Desenvolvimento Regional (FEDER). Personal Grants: SFRH/BPD/33036/2006 to AC; SFRH/BD/33573/2009

Details

ISSN :
16643224
Volume :
6
Database :
OpenAIRE
Journal :
Frontiers in Immunology
Accession number :
edsair.doi.dedup.....28caf8f9bd0595c7b0a44f1fcfe79086