IL-17A Promotes Intracellular Growth of Mycobacterium by Inhibiting Apoptosis of Infected Macrophages.
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.
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal ; ICVS/3B's - PT Government Associate Laboratory, University of Minho , Braga , Portugal.
Andrea
A
Cruz
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal ; ICVS/3B's - PT Government Associate Laboratory, University of Minho , Braga , Portugal.
Paula
P
Ludovico
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal ; ICVS/3B's - PT Government Associate Laboratory, University of Minho , Braga , Portugal ; Trudeau Institute , Saranac Lake, NY , USA.
Egidio
E
Torrado
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal ; ICVS/3B's - PT Government Associate Laboratory, University of Minho , Braga , Portugal.
José Bernardo
JB
Gama
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal ; ICVS/3B's - PT Government Associate Laboratory, University of Minho , Braga , Portugal.
Jeremy
J
Sousa
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal ; ICVS/3B's - PT Government Associate Laboratory, University of Minho , Braga , Portugal.
Joana
J
Gaifem
Department of Immunophysiology, University of Porto , Porto , Portugal.
Rui
R
Appelberg
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal ; ICVS/3B's - PT Government Associate Laboratory, University of Minho , Braga , Portugal.
Fernando
F
Rodrigues
Trudeau Institute , Saranac Lake, NY , USA.
Andrea M
AM
Cooper
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal ; ICVS/3B's - PT Government Associate Laboratory, University of Minho , Braga , Portugal.
Jorge
J
Pedrosa
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal ; ICVS/3B's - PT Government Associate Laboratory, University of Minho , Braga , Portugal.
Margarida
M
Saraiva
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal ; ICVS/3B's - PT Government Associate Laboratory, University of Minho , Braga , Portugal.
António G
AG
Castro
IL-17; apoptosis; macrophages; mycobacteria; p53