Systemic effects in naive mice injected with immunomodulatory lectin ArtinM

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 mu g) in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naive BALB/c mice. The mice were s.c. injected twice (7 days interval) with ArtinM (0.5, 1.0, 2.5, or 5.0 mu g), 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 mu g). Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses >= 2.5 mu g. 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-gamma, TNF-alpha, 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 mu g ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naIve mice, whereas the relative expressions of Tbet, GATA-3, and ROR-gamma t were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naIve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naive mice.