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Alternatively Activated Macrophages Elicited by Helminth Infection Can Be Reprogrammed to Enable Microbial Killing1
 

Summary: Alternatively Activated Macrophages Elicited by Helminth
Infection Can Be Reprogrammed to Enable Microbial Killing1
Katie J. Mylonas,2
Meera G. Nair,2,3
Lidia Prieto-Lafuente, Daniel Paape, and Judith E. Allen4
The prime function of classically activated macrophages (activated by Th1-type signals, such as IFN- ) is microbial de-
struction. Alternatively activated macrophages (activated by Th2 cytokines, such as IL-4 and IL-13) play important roles in
allergy and responses to helminth infection. We utilize a murine model of filarial infection, in which adult nematodes are
surgically implanted into the peritoneal cavity of mice, as an in vivo source of alternatively activated macrophages. At 3 wk
postinfection, the peritoneal exudate cell population is dominated by macrophages, termed nematode-elicited macrophages
(NeM ), that display IL-4-dependent features such as the expression of arginase 1, RELM- (resistin-like molecule ), and
Ym1. Since increasing evidence suggests that macrophages show functional adaptivity, the response of NeM to proinflam-
matory Th1-activating signals was investigated to determine whether a switch between alternative and classical activation
could occur in macrophages differentiated in an in vivo infection setting. Despite the long-term exposure to Th2 cytokines
and antiinflammatory signals in vivo, we found that NeM were not terminally differentiated but could develop a more
classically activated phenotype in response to LPS and IFN- . This was reflected by a switch in the enzymatic pathway for
arginine metabolism from arginase to inducible NO synthase and the reduced expression of RELM- and Ym1. Further-
more, this enabled NeM to become antimicrobial, as LPS/IFN- -treated NeM produced NO that mediated killing of
Leishmania mexicana. However, the adaptation to antimicrobial function did not extend to key regulatory pathways, such as
IL-12 production, which remained unaltered. The Journal of Immunology, 2009, 182: 30843094.

  

Source: Allen, Judith - School of Biological Sciences, University of Edinburgh

 

Collections: Biology and Medicine