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Immunology - Infectious Diseases - Neurological Disorders - Physiology

Type II-Activated Murine Macrophages Produce IL-4
Published: Friday, October 05, 2012
Author: Anne Camille La Flamme et al.

by Anne Camille La Flamme, Marie Kharkrang, Sarrabeth Stone, Sara Mirmoeini, Delgertsetseg Chuluundorj, Ryan Kyle


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-4Ra-deficient mice to be classically or type II-activated in vitro.


We found that although both WT and IL-4Ra-deficient macrophages could be classically activated by LPS or type II activated by immune complexes plus LPS, IL-4Ra-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-4Ra-/- 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.


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.