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