%0 Journal Article
%T Type II-Activated Murine Macrophages Produce IL-4
%A Anne Camille La Flamme
%A Marie Kharkrang
%A Sarrabeth Stone
%A Sara Mirmoeini
%A Delgertsetseg Chuluundorj
%A Ryan Kyle
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0046989
%X Background Type II activation of macrophages is known to support Th2 responses development; however, the role of Th2 cytokines (esp. IL-4) on type II activation is unknown. To assess whether the central Th2 cytokine IL-4 can alter type II activation of macrophages, we compared the ability of bone marrow-derived macrophages from wild type (WT) and IL-4R¦Á-deficient mice to be classically or type II-activated in vitro. Results We found that although both WT and IL-4R¦Á-deficient macrophages could be classically activated by LPS or type II activated by immune complexes plus LPS, IL-4R¦Á-deficient macrophages consistently produced much higher levels of IL-12p40 and IL-10 than WT macrophages. Additionally, we discovered that type II macrophages from both strains were capable of producing IL-4; however, this IL-4 was not responsible for the reduced IL-12p40 and IL-10 levels produced by WT mice. Instead, we found that derivation culture conditions (GM-CSF plus IL-3 versus M-CSF) could explain the different responses of BALB/c and IL-4R¦Á£¿/£¿ macrophages, and these cytokines shaped the ensuing macrophage such that GM-CSF plus IL-3 promoted more IL-12 and IL-4 while M-CSF led to higher IL-10 production. Finally, we found that enhanced IL-4 production is characteristic of the type II activation state as other type II-activating products showed similar results. Conclusions Taken together, these results implicate type II activated macrophages as an important innate immune source of IL-4 that may play an important role in shaping adaptive immune responses.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0046989