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(Journal of Leukocyte Biology. 2002;71:271-278.)
© 2002 by Society for Leukocyte Biology

Macrophages from IL-12p40-deficient mice have a bias toward the M2 activation profile

Karina R. B. Bastos^*, José M. Alvarez^*, Cláudio R. F. Marinho^*, Luiz V. Rizzo^*, and Maria Regina D’Império Lima^*

^* Department of Immunology, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil; and
Fundação E. J. Zerbini, São Paulo, Brazil

Correspondence: Dr. Maria Regina D’Império Lima, Departamento de Imunologia, ICB, Av. Prof. Lineu Prestes, 1730, Universidade de São Paulo, São Paulo, SP, Brazil, CEP-05508-900. E-mail: relima{at}usp.br

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-ß1, 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-ß1 and responding to rIFN- 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-ß1 is directly implicated in sustaining the M2 profile because its inhibition increases NO release from IL-12p40KO macrophages. IFN- deficiency is apparently not the reason for TGF-ß1 up-regulation, because rIFN-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.

Key Words: macrophage polarization • TGF-ß1 • nitric oxide • IL-12p40KO • Trypanosoma cruzi

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