help button home button Am J Pathol PCR Enhanced. PCRboost from Biomatrica
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
A more recent version of this article appeared on August 1, 2008

Published online before print July 3, 2008
This Article
Right arrow Full Text (Rapid PDF)
Right arrow All Versions of this Article:
ajpath.2008.080126v1
173/2/423    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Coltri, K. C.
Right arrow Articles by Roque-Barreira, M.-C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coltri, K. C.
Right arrow Articles by Roque-Barreira, M.-C.
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.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2008 by the American Society for Investigative Pathology.