Therapeutic administration of KM+ lectin protects mice against Paracoccidioides brasiliensis infection via interleukin-12 production in a Toll-like receptor 2-dependent mechanism


Autoria(s): COLTRI, Kely C.; OLIVEIRA, Leandro L.; PINZAN, Carnila F.; VENDRUSCOLO, Patricia E.; MARTINEZ, Roberto; GOLDMAN, Maria Helena; PANUNTO-CASTELO, Ademilson; ROQUE-BARREIRA, Maria-Cristina
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2008

Resumo

KM+ is a mannose-binding lectin from Artocarpus integrifolia that induces interleukin (IL)-12 production by macrophages and protective T helper I 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-a, 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.

Identificador

AMERICAN JOURNAL OF PATHOLOGY, v.173, n.2, p.423-432, 2008

0002-9440

http://producao.usp.br/handle/BDPI/20701

10.2353/ajpath.2008.080126

http://dx.doi.org/10.2353/ajpath.2008.080126

Idioma(s)

eng

Publicador

AMER SOC INVESTIGATIVE PATHOLOGY, INC

Relação

American Journal of Pathology

Direitos

closedAccess

Copyright AMER SOC INVESTIGATIVE PATHOLOGY, INC

Palavras-Chave #N-LINKED GLYCOSYLATIONS #NITRIC-OXIDE SYNTHASE #T-CELL SUBSETS #ARTOCARPUS-INTEGRIFOLIA #DENDRITIC CELLS #PULMONARY PARACOCCIDIOIDOMYCOSIS #FUNGICIDAL ACTIVITY #MONONUCLEAR-CELLS #IMMUNE-RESPONSES #INTERFERON-GAMMA #Pathology
Tipo

article

original article

publishedVersion