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Glycobiology, 2001, Vol. 11, No. 12 1035-1042
© 2001 Oxford University Press

KM+, a lectin from Artocarpus integrifolia, induces IL-12 p40 production by macrophages and switches from type 2 to type 1 cell-mediated immunity against Leishmania major antigens, resulting in BALB/c mice resistance to infection

Ademilson Panunto-Castelo1,3,5, Maria A. Souza1,5,6, Maria-Cristina Roque-Barreira2,3,5 and João S. Silva4,5

3Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP 14040-900, Brazil; 4Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP 14040-900, Brazil; 5Pós-graduação em Imunologia Básica e Aplicada, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP 14040-900, Brazil; and 6Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG 38400-902, Brazil

The outcome and severity of some diseases correlate with the dominance of either the T helper 1 (Th1) or Th2 immune response, which is stimulated by IL-12 or IL-4, respectively. In the present study we demonstrate that gamma interferon (IFN-{gamma}) secretion by murine spleen cells stimulated with KM+, a mannose-binding lectin from Artocarpus integrifolia, is due to IL-12 induction, because (1) macrophages from several sources (including cell lines) produced IL-12 p40 in response to KM+, and (2) lectin-free supernatants from J774 cell line cultures stimulated with KM+ induced the secretion of IFN-{gamma} by spleen cell cultures, an effect blocked by the supernatant pretreatment with anti-IL-12 antibody. The known pattern of susceptibility of BALB/c mice to infection with Leishmania major, attributed to high levels of IL-4 production leading to a Th2 nonprotective immune response, was modified by administration of KM+. Draining lymph node cells from these immunized BALB/c mice (in contrast to cells from animals immunized only with soluble leishmanial antigen [SLA]) secreted high levels of IFN-{gamma} and low levels of IL-4, which characterized a Th1 rather than a Th2 response pattern. The footpad thickness of BALB/c mice immunized with SLA plus KM+ and challenged with L. major was similar to that of uninfected mice. This beneficial effect against leishmanial infection was blocked by pretreatment of these mice with anti-IL-12 antibody. These observations indicate that KM+ induces IL-12 p40 in vivo and has a protective effect against L. major infection.

1 These authors contributed equally to this work.

2 To whom correspondence should be addressed


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