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Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial-induced signalling and cytokine secretion.

Abstract : Alternatively activated macrophages play an important role in host defense in the context of a T helper type 2 (Th2) microenvironment such as parasitic infection. However, the role of these macrophages during secondary challenge with Th1 pathogens is poorly defined. In this study, thioglycollate-elicited mouse peritoneal macrophages were treated with interleukin-4 (IL-4) or IL-13 in vitro and challenged with Neisseria meningitidis. After 8 to 12 hours of IL-4 pretreatment, the nonopsonic phagocytic uptake of N meningitidis was markedly reduced, depending on the common IL-4Ralpha chain, but independent of Scavenger receptor A and macrophage receptor with collagenous structure (MARCO), 2 known receptors for N meningitidis. Inhibition of phagocytosis extended to several other microbial particles, zymosan, and other bacteria. Concomitantly, IL-4 potentiated the secretion of proinflammatory cytokines, after additional bacterial stimulation, which depended on the MyD88 signaling pathway. Similar results were obtained after intraperitoneal stimulation of IL-4 and N meningitidis in vivo. Further in vitro studies showed a striking correlation with inhibition of Akt phosphorylation and stimulation of the mitogen-activated protein kinase pathway; inhibition of phagocytosis was associated with inhibition of phagosome formation. These findings are relevant to host defense in mixed infections within a Th2 microenvironment and shed light on immunologic functions associated with alternative priming and full activation of macrophages.
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https://hal.archives-ouvertes.fr/hal-00474829
Contributor : Murielle Humbert <>
Submitted on : Wednesday, April 21, 2010 - 12:46:26 AM
Last modification on : Thursday, February 15, 2018 - 8:48:14 AM

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Audrey Varin, Subhankar Mukhopadhyay, Georges Herbein, Siamon Gordon. Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial-induced signalling and cytokine secretion.. Blood, American Society of Hematology, 2010, 115 (2), pp.353-62. ⟨10.1182/blood-2009-08-236711⟩. ⟨hal-00474829⟩

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