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IL-17A Promotes Intracellular Growth of Mycobacterium by Inhibiting Apoptosis of Infected Macrophages
- 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
- Subjects :
- p53
lcsh:Immunologic diseases. Allergy
Ciências Médicas::Ciências da Saúde
Ciências da Saúde [Ciências Médicas]
mycobacteria
Medicina Básica [Ciências Médicas]
Immunology
Apoptosis
Mitochondrion
03 medical and health sciences
0302 clinical medicine
Immunity
IL-17A
Immunology and Allergy
Macrophage
Original Research
030304 developmental biology
0303 health sciences
Mycobacterium bovis
Science & Technology
biology
Macrophages
Cytochrome c
Mycobacteria
biology.organism_classification
3. Good health
Cell biology
IL-17
Ciências Médicas::Medicina Básica
biology.protein
lcsh:RC581-607
Intracellular
030215 immunology
Mycobacterium
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....28caf8f9bd0595c7b0a44f1fcfe79086