Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

Abstract

Toll-like receptors (TLR) contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from Artocarpus heterophyllus interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c.) ArtinM (0.5 μg) in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naïve BALB/c mice. The mice were s.c. injected twice (7 days interval) with ArtinM (0.5, 1.0, 2.5, or 5.0 μg), LPS (positive control), or PBS (negative control) and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 μg). Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ≥2.5 μg. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB) and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-γ, TNF-α, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 μg ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naïve mice, whereas the relative expressions of T-bet, GATA-3, and ROR-γt were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naïve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naïve mice.

iNOS/Arginase-1 expression in the pulmonary tissue over time duringCryptococcus gattiiinfection

“…The supernatants were used for the measurement of IL-12p40, TNF-α, IFN-γ, IL-10 and IL-17 levels by ELISA according to the manufacturer’s protocol using Ab pairs purchased from BD Biosciences (Pharmingen, San Diego, CA), as previously described. 26,27 Concentrations were determined relative to standard curves prepared from recombinant murine cytokines. Absorbances were read at 450 nm in a PowerWave X microplate scanning spectrophotometer (BioTek Instruments, Inc.).…”

The lectin ArtinM activates RBL-2H3 mast cells without inducing degranulation

“…ArtinM has the potential to act as an immunomodulator in microbial infections [5,35,36]. It exerts a protective effect against Paracoccidioides brasiliensis infection by promoting the development of a Th1 immune response.…”

The Response of IL-17-Producing B Cells to ArtinM Is Independent of Its Interaction with TLR2 and CD14

“…Our group has been investigating the direct effect of ArtinM on murine T cells in order to understand the mechanisms involved in the immunomodulatory activity triggered by ArtinM [ 21 , 22 , 30 , 31 ], and the capacity of ArtinM to induce IL-17 production in spleen cells and CD4 + T cells was recently reported [ 21 ]. Interestingly, we found reduced levels of IL-17 induced by ArtinM in spleen cells after B-cell depletion [ 21 ], and the polyclonal activation of B cells induced by ArtinM was verified in naïve mice that received ArtinM at various doses [ 32 ]. Thus, these findings suggest the involvement of B cells in the immunomodulatory activity induced by ArtinM.…”