en
Scientific article
English

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

Published inJournal of leukocyte biology, vol. 86, no. 1, p. 81-90
Publication date2009
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
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. doi: 10.1189/jlb.1008590
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Article (Published version)
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ISSN of the journal0741-5400
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