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

Chakour, Reza; Allenbach, Cindy; Desgranges, Florian; Charmoy, Mélanie; Mauel, Jacques; Garcia, Irène; Launois, Pascal; Louis, Jacques; Tacchini-Cottier, Fabienne

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Title		A new function of the Fas-FasL pathway in macrophage activation
Authors		Chakour, Reza Allenbach, Cindy Desgranges, Florian Charmoy, Mélanie Mauel, Jacques Garcia, Irène Launois, Pascal Louis, Jacques Tacchini-Cottier, Fabienne show all authors [1 - 9]
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		Animals — Antigens, CD95/metabolism — Fas Ligand Protein/pharmacology — Interferon-gamma/pharmacology — Interleukin-4/pharmacology — Leishmania major/immunology — Macrophage Activation — Macrophages/parasitology/secretion — Mice — Mice, Inbred BALB C — Signal Transduction/immunology
Identifiers		DOI: 10.1189/jlb.1008590 PMID: 19380712
Full text		Article (Published version) (496 Kb) - Limited access to UNIGE Other version: http://www.jleukbio.org/cgi/content/full/86/1/81
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Rôles des cytokines de la famille du TNF dans les infections mycobactériennes (500)
Citation (ISO format)		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. https://archive-ouverte.unige.ch/unige:5459