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Macrophages from IL‐12p40‐deficient mice have a bias toward the M2 activation profile
Author(s) -
Bastos Karina R. B.,
Alvarez José M.,
Marinho Cláudio R. F.,
Rizzo Luiz V.,
D’Império Lima Maria Regina
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.71.2.271
Subject(s) - biology , macrophage , intracellular , cytokine , microbiology and biotechnology , interleukin 4 , macrophage polarization , transforming growth factor beta , interleukin 10 , knockout mouse , immunology , transforming growth factor , gene , in vitro , genetics
Recent studies have provided evidence that macrophages from Th1‐prone mouse strains respond with an M1 profile, and macrophages from Th2‐prone mouse strains respond with an M2 profile, characterized by the dominant production of NO or TGF‐β1, respectively. We have shown that peritoneal macrophages from IL‐12p40 gene knockout mice have a bias toward the M2 profile, spontaneously secreting large amounts of TGF‐β1 and responding to rIFN‐γ with weak NO production. Moreover, IL‐12p40KO macrophages are more permissive to Trypanosoma cruzi replication than their wild‐type littermate cells. Prolonged incubation with rIL‐12 fails to reverse the M2 polarization of IL‐12p40KO macrophages. However, TGF‐β1 is directly implicated in sustaining the M2 profile because its inhibition increases NO release from IL‐12p40KO macrophages. IFN‐γ deficiency is apparently not the reason for TGF‐β1 up‐regulation, because rIFN‐γKO macrophages produce normal amounts of this cytokine. These findings raise the possibility that IL‐12 has a central role in driving macrophage polarization, regulating their intrinsic ability to respond against intracellular parasites.