KM+, a lectin from Artocarpus integrifolia, induces IL-12 p40 production by macrophages and switches from type 2 to type 1 cell-mediated immunity against Leishmania major antigens, resulting in BALB/c mice resistance to infection

Abstract

The outcome and severity of some diseases correlate with the dominance of either the T helper 1 (Th1) or Th2 immune response, which is stimulated by IL-12 or IL-4, respectively. In the present study we demonstrate that gamma interferon (IFN-gamma) secretion by murine spleen cells stimulated with KM(+), a mannose-binding lectin from Artocarpus integrifolia, is due to IL-12 induction, because (1) macrophages from several sources (including cell lines) produced IL-12 p40 in response to KM(+), and (2) lectin-free supernatants from J774 cell line cultures stimulated with KM(+) induced the secretion of IFN-gamma by spleen cell cultures, an effect blocked by the supernatant pretreatment with anti-IL-12 antibody. The known pattern of susceptibility of BALB/c mice to infection with Leishmania major, attributed to high levels of IL-4 production leading to a Th2 nonprotective immune response, was modified by administration of KM(+). Draining lymph node cells from these immunized BALB/c mice (in contrast to cells from animals immunized only with soluble leishmanial antigen [SLA]) secreted high levels of IFN-gamma and low levels of IL-4, which characterized a Th1 rather than a Th2 response pattern. The footpad thickness of BALB/c mice immunized with SLA plus KM(+) and challenged with L. major was similar to that of uninfected mice. This beneficial effect against leishmanial infection was blocked by pretreatment of these mice with anti-IL-12 antibody. These observations indicate that KM(+) induces IL-12 p40 in vivo and has a protective effect against L. major infection.

Protective effect of lectin from Synadenium carinatum on Leishmania amazonensis infection in BALB/c mice

“…In the present study, IL-12 and IFN-γ were expressed in the lesion, which is in agreement with the findings of other authors who had shown that these 2 cytokines are important for the development of protective immune responses in experimental leishmaniasis (Panunto-Castelo et al, 2001;Hernández et al, 2006). The ample expression of iNOS by immunized animals suggests that there was production of nitric oxide (NO) in the lesion, leading us to believe that the NO, together with IL-12 and TNF-α, acts in an important and synergistic way in mediation of the local inflammatory process.…”

“…The lectins are widely distributed in nature in seeds, leaves, barks, bulbs, rhizomes, roots, cotyledon and tubers depending on the plant species. Lectins, such as the ConBr from Canavalia braziliensis and KM+ from Artocarpus integrifolia induce IFN-γ and IL-12 p40 production and promote an inversion of the Th2 to Th1 cytokine pattern in BALB/c mice infected with L. amazonensis and L. major, respectively (Barral-Netto et al, 1996;Panunto-Castelo et al, 2001). Saponins, such as from Quillaja spp, Quillaja saponaria, and the conformational isomers of QuilA sapogenin, have been shown to increase the cutaneous response to Leishmania antigens and enhance serum levels of IFN-γ, and may protect against murine infections with L. major, L. donovani and Leishmania chagasi Palatnik de Sousa et al, 2004;Oliveira-Freitas et al, 2006).…”

The Novel Cytokine p43 Induces IL-12 Production in Macrophages via NF-κB Activation, Leading to Enhanced IFN-γ Production in CD4+ T Cells

“…7). The addition of anti-IL-12 mAb to mannose-binding lectin-treated macrophage cultures restored the induction of IL-4 and inhibited the induction of IFN-␥ synthesis by T cells (41). In contrast, p43 had no effect on the production of IL-4 in lymph node cells (Fig.…”

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

“…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.…”