| First Author | Bastos KR | Year | 2002 |
| Journal | J Leukoc Biol | Volume | 71 |
| Issue | 2 | Pages | 271-8 |
| PubMed ID | 11818448 | Mgi Jnum | J:74693 |
| Mgi Id | MGI:2158977 | Citation | Bastos KR, et al. (2002) Macrophages from IL-12p40-deficient mice have a bias toward the M2 activation profile. J Leukoc Biol 71(2):271-8 |
| abstractText | 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. |
