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

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-␥, and tumor necrosis factor-␣, 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.

Inhibition of Hepatocarcinogenesis by ArtinM via Anti-proliferative and Pro-apoptotic Mechanisms

“…Moreover, ArtinM treatment triggered a higher TNFα mRNA expression in animals exposed to DEN compared to animals exposed to just DEN. This finding is in accordance to previous studies, which demonstrated that ArtinM induces the TNFα pathway (13,17,44). Since TNFα is involved in apoptosis during hepatocarcinogenesis (43), induced TNFα mRNA expression by ArtinM may explain the increased number of apoptotic preneoplastic hepatocytes observed in the present study.…”

“…Previous studies have reported that lymphocytes and natural killer (NK) cells can produce IFNγ with anti-tumor activity (45). Although ArtinM had previously been demonstrated in murine models of infection to stimulate IFNγ expression (13,15,17), the present study is the first to detect a significant increase in mRNA expression of IFNγ in response to ArtinM treatment during hepatocarcinogenesis. Increased IFNγ expression was accompanied by a reduction of preneoplastic foci.…”

“…ArtinM is a d-mannose-binding lectin found in the seeds of Artocarpus heterophyllus that interacts with N-glycans and is associated with receptors on the surface of phagocytic cells to induce production of inflammatory mediators, such as tumor necrosis factor alpha (TNFα) (13), interleukin 12 (IL12) and interferon gamma (IFNγ) (14). Moreover, the protective effect of ArtinM against intracellular pathogens (15,16,17) and against the development of hematopoietic cancer (18) is well-known. However, it is necessary to investigate the effects of ArtinM against neoplastic progression in vivo.…”

Jackfruit (Artocarpus heterophyllus) seed extract exhibits fibrino(geno)lytic activity

“…Jackfruit seeds are reported to contain the highest amount of trypsin, chymotrypsin, elastase inhibitors and lectin family glycoprotein's (Jacalin). [12][13][14] For instance, Jacalin (immuno modulatory glycoprotein) is one of the most important lectin characterized so far from Jackfruit seeds, however, the proteolytic enzymes were least explored. 15 However Siritapetawee et al (2012) reported on antimicrobial protease (AMP48) and novel serine protease having fibrino (geno) lytic activities from Artocarpus heterophyllus latex.…”

Avaliação terapêutica da formulação vacinal baseada no peptídeo P10 derivado da glicoproteína (gp43) de Paracoccidioides brasiliensis e na flagelina de Salmonella (FliCd).

“…Análise por One-way ANOVA seguida de pós-teste de Tukey. (TABORDA et al, 1998;MARQUES et al, 2006;BUISSA-FILHO et al, 2008;RITTNER, 2008 Langerhans, e consequentemente promover ativação de respostas imunológicas capazes de conter a propagação da doença já estabelecida (MARQUES et al, 2006;COLTRI et al, 2008;AMARAL et al, 2010).…”