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Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial-induced signalling and cytokine secretion by Audrey Varin, Subhankar Mukhopadhyay, Georges Herbein, and Siamon Gordon Blood Volume 115(2):353-362 January 14, 2010 ©2010 by American Society of Hematology

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

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Page 1: Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial- induced signalling and cytokine secretion by

Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial-

induced signalling and cytokine secretion

by Audrey Varin, Subhankar Mukhopadhyay, Georges Herbein, and Siamon Gordon

BloodVolume 115(2):353-362

January 14, 2010

©2010 by American Society of Hematology

Page 2: Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial- induced signalling and cytokine secretion by

Alternative activation of MΦs decreases N meningitidis uptake.

Audrey Varin et al. Blood 2010;115:353-362

©2010 by American Society of Hematology

Page 3: Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial- induced signalling and cytokine secretion by

IL-4 priming of MΦs does not modify SRA and MARCO expression or decrease N meningitidis binding at MΦ surface.

Audrey Varin et al. Blood 2010;115:353-362

©2010 by American Society of Hematology

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

Alternative activation potentiates N meningitidis–induced proinflammatory cytokine secretion via MyD88, independent of SRA and MARCO. (A) WT ThioMΦs were cultivated 48 hours in the

presence or absence of IL-4 and incubated for 24 hours with or without N men...

Audrey Varin et al. Blood 2010;115:353-362

©2010 by American Society of Hematology

Page 5: Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial- induced signalling and cytokine secretion by

IL-4 impairs uptake of RdGnX-N meningitidis and increases antibacterial proinflammatory response in vivo.

Audrey Varin et al. Blood 2010;115:353-362

©2010 by American Society of Hematology

Page 6: Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial- induced signalling and cytokine secretion by

IL-4 pretreatment and N meningitidis challenge inhibit Akt phosphorylation, but stimulate p42/p44 and p38 pathways.

Audrey Varin et al. Blood 2010;115:353-362

©2010 by American Society of Hematology

Page 7: Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial- induced signalling and cytokine secretion by

Microscopy analysis of zymosan phagocytosis by untreated and IL-4–treated ThioMΦs.

Audrey Varin et al. Blood 2010;115:353-362

©2010 by American Society of Hematology

Page 8: Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial- induced signalling and cytokine secretion by

Schematic summary of effect of IL-4 priming on phagocytic and secretory capacities of MΦs.

Audrey Varin et al. Blood 2010;115:353-362

©2010 by American Society of Hematology