Macrophages from IL-12p40-deficient mice have a bias toward the M2 activation profile.
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-beta 1, 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-beta 1 and responding to rIFN-gamma 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-beta 1 is directly implicated in sustaining the M2 profile because its inhibition increases NO release from IL-12p40KO macrophages. IFN-gamma deficiency is apparently not the reason for TGF-beta 1 up-regulation, because rIFN-gamma KO 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.
Bastos
Karina R B
KR
Department of Immunology, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
Alvarez
José M
JM
Marinho
Cláudio R F
CR
Rizzo
Luiz V
LV
Lima
Maria Regina D'Império
MR
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics; D008262:Macrophage Activation / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis*; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma