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A new function of the Fas-FasL pathway in macrophage activation

Chakour, Reza
Allenbach, Cindy
Desgranges, Florian
Charmoy, Mélanie
Mauel, Jacques
Launois, Pascal
Louis, Jacques
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Published in Journal of Leukocyte Biology. 2009, vol. 86, no. 1, p. 81-90
Abstract Upon infection with the protozoan parasite Leishmania major, susceptible BALB/c mice develop unhealing lesions associated with the maturation of CD4(+)Th2 cells secreting IL-4. In contrast, resistant C57BL/6 mice heal their lesions, because of expansion and secretion of IFN-gamma of CD4(+) Th1 cells. The Fas-FasL pathway, although not involved in Th cell differentiation, was reported to be necessary for complete resolution of lesions. We investigate here the role of IFN-gamma and IL-4 on Fas-FasL nonapoptotic signaling events leading to the modulation of macrophage activation. We show that addition of FasL and IFN-gamma to BMMø led to their increased activation, as reflected by enhanced secretion of TNF, IL-6, NO, and the induction of their microbicidal activity, resulting in the killing of intracellular L. major. In contrast, the presence of IL-4 decreased the synergy of IFN-gamma/FasL significantly on macrophage activation and the killing of intracellular L. major. These results show that FasL synergizes with IFN-gamma to activate macrophages and that the tight regulation by IFN-gamma and/or IL-4 of the nonapoptotic signaling events triggered by the Fas-FasL pathway affects significantly the activation of macrophages to a microbicidal state and may thus contribute to the pathogenesis of L. major infection.
Keywords AnimalsAntigens, CD95/metabolismFas Ligand Protein/pharmacologyInterferon-gamma/pharmacologyInterleukin-4/pharmacologyLeishmania major/immunologyMacrophage ActivationMacrophages/parasitology/secretionMiceMice, Inbred BALB CSignal Transduction/immunology
PMID: 19380712
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Other version: http://www.jleukbio.org/cgi/content/full/86/1/81
Research group Rôles des cytokines de la famille du TNF dans les infections mycobactériennes (500)
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CHAKOUR, Reza et al. A new function of the Fas-FasL pathway in macrophage activation. In: Journal of Leukocyte Biology, 2009, vol. 86, n° 1, p. 81-90. doi: 10.1189/jlb.1008590 https://archive-ouverte.unige.ch/unige:5459

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Deposited on : 2010-03-17

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