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A more recent version of this article appeared on August 1, 2008

Published online before print July 3, 2008
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Copyright © 2008 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2008.080126

Accepted for publication May 13, 2008.

Article

Therapeutic Administration of KM+ Lectin Protects Mice Against Paracoccidioides brasiliensis Infection via Interleukin-12 Production in a Toll-Like Receptor 2-Dependent Mechanism

Kely C. Coltri*, Leandro L. Oliveira*, Camila F. Pinzan*, Patrícia E. Vendruscolo*, Roberto Martinez{dagger}, Maria Helena Goldman{ddagger}, Ademilson Panunto-Castelo{sect}, and Maria-Cristina Roque-Barreira*@

From Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos,* Faculdade de Medicina de Ribeirão Preto, Departamento de Clínica Médica,{dagger} Faculdade de Medicina de Ribeirão Preto, Departamento de Biologia,{ddagger} Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, and Departamento de Enfermagem Geral e Especializada,{sect} Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil

@ To whom correspondence should be addressed. E-mail: mcrbarre{at}fmrp.usp.br.


  Abstract

KM+ is a mannose-binding lectin from Artocarpus integrifolia that induces interleukin (IL)-12 production by macrophages and protective T helper 1 immune response against Leishmania major infection. In this study, we performed experiments to evaluate the therapeutic activity of jackfruit KM+ (jfKM+) and its recombinant counterpart (rKM+) in experimental paracoccidioidomycosis. To this end, jfKM+ or rKM+ was administered to BALB/c mice 10 days after infection with Paracoccidiodes brasiliensis. Thirty days postinfection, lungs from the KM+-treated mice contained significantly fewer colony-forming units and little to no organized granulomas compared to the controls. In addition, lung homogenates from the KM+-treated mice presented higher levels of nitric oxide, IL-12, interferon-{gamma}, and tumor necrosis factor-{alpha}, whereas higher levels of IL-4 and IL-10 were detected in the control group. With mice deficient in IL-12, Toll-like receptor (TLR) 2, TLR4, or TLR adaptor molecule MyD88, we demonstrated that KM+ led to protection against P. brasiliensis infection through IL-12 production, which was dependent on TLR2. These results demonstrated a beneficial effect of KM+ on the severity of P. brasiliensis infection and may expand its potential use as a novel immunotherapeutic molecule.






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Copyright © 2008 by the American Society for Investigative Pathology.