Type II-activated murine macrophages produce IL-4.
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-4Rα-deficient mice to be classically or type II-activated in vitro.


RESULTS
We found that although both WT and IL-4Rα-deficient macrophages could be classically activated by LPS or type II activated by immune complexes plus LPS, IL-4Rα-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-4Rα-/- 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.
School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand. anne.laflamme@vuw.ac.nz
Anne Camille
AC
La Flamme
Marie
M
Kharkrang
Sarrabeth
S
Stone
Sara
S
Mirmoeini
Delgertsetseg
D
Chuluundorj
Ryan
R
Kyle
D000818:Animals; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D053662:Interleukin-4 Receptor alpha Subunit
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016753:Interleukin-10; D007377:Interleukin-3; D015847:Interleukin-4; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; C556062:IL10 protein, mouse; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit