Therapeutic administration of KM+ lectin protects mice against Paracoccidioides brasiliensis infection via interleukin-12 production in a toll-like receptor 2-dependent mechanism.
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.
Coltri
Kely C
KC
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900-Ribeirão Preto, São Paulo, Brazil.
Oliveira
Leandro L
LL
Pinzan
Camila F
CF
Vendruscolo
Patrícia E
PE
Martinez
Roberto
R
Goldman
Maria Helena
MH
Panunto-Castelo
Ademilson
A
Roque-Barreira
Maria-Cristina
MC
D000818:Animals; D031622:Artocarpus; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D037181:Lectins, C-Type / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010228:Paracoccidioides / Q000187:drug effects*; D010229:Paracoccidioidomycosis / Q000188:drug therapy* / Q000378:metabolism; D037121:Plant Lectins / Q000494:pharmacology / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D037121:Plant Lectins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D018664:Interleukin-12; D009569:Nitric Oxide