Protective effect of Artin M from extract of Artocarpus integrifolia seeds by Th1 and Th17 immune response on the course of infection by Candida albicans

Abstract

The immunoregulatory effect of Artin M and jacalin from extract of Artocarpus integrifolia seeds (jack extract) against infection with Candida albicans was investigated. Swiss mice received jack extract containing 500 μg protein/ml PBS intraperitoneally (i.p.) or PBS alone and after 72 h were infected i.p. with C. albicans CR15 (10(7)) and sacrificed after 30 min, 2, 6, 24, and 72 h. ELISA analysis revealed that in jack extract-treated mice IFN-γ was predominantly produced versus IL-10 in control mice. These results suggest that jack extract induced a protective immune response, since C. albicans clearance was complete at 72 h postinfection. Jack extract presents two lectins (Artin M and jacalin) with distinct biological properties. Artin M was able to induce IL-12 production by macrophages. Also, Artin M in different concentrations, associated with jacalin or in jack extract induced both IFN-γ and IL-17 production. As a consequence, phagocytic and candidacidal activity increased significantly. Alanine aminotransferase activity (ALT) was used as parameter for damage of the liver. The activity of ALT correlated with inoculum size that increased significantly in control group, however, mice pretreated with jack extract 3 days before infection presented normal ALT. Mice pretreated with jack extract that received a lethal inoculum of Candida presented 90% survival versus 20% among controls or mice pretreated with jacalin. Thus, the results suggest that Artin M by itself, associated with jacalin or present in jack extract is able to induce protective Th1 and Th17 immune responses against Candida albicans infection.

Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM

“…The administration of ArtinM to mice consistently conferred protection against infections by intracellular pathogens. The Th1-skewed response induced by ArtinM is balanced by the induction of IL-10 production, which prevents exacerbated inflammation [12][13][14][15]. As showed in the present study, the IL-10 inducing property was also demonstrated by y-ArtinM.…”

“…Systemic administration of ArtinM induces Th1 immunity that confers protection against various intracellular pathogens [10,[12][13][14][15]. Topical administration of ArtinM promotes regeneration of injured corneal epithelium and oral mucosa [16,17].…”

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

“…ArtinM is also associated in the stimulation of IL12 production (14). However, in this study no effect was observed in the IL12 mRNA expression by ArtinM treatment.…”

“…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.…”

Artin M enhances TNF-α production and phagocytosis of Candida albicans mediated by dectin-1 and mannose receptors

“…In a previous work, our group verified differential properties of Artin M and jacalin present in an extract of A. integrifolia; jacalin treatment was unable to induce protective immune response and few mice survived a lethal inoculum of C. albicans, whereas Artin M was able to induce Th1 and Th17 protective immune responses, by itself or associated with jacalin [18]. Our group has demonstrated high levels of IFN-γ and IL-17 6 h postinfection in these mice and that Artin M but not jacalin induced TNF-α and IL-12 production by macrophages in vitro.…”