Barley beta-Glucan and Zymosan induce Dectin-1 and Toll-like receptor 2 co-localization and anti-leishmanial immune response in Leishmania donovani-infected BALB/c mice

Abstract

Toll-like receptors (TLRs), TLR2 in particular, are shown to recognize various glycans and glycolipid ligands resulting in various immune effector functions. As barley β-glucan and zymosan are the glycans implicated in immunomodulation, we examined whether these ligands interact with Dectin-1, a lectin-type receptor for glycans, and TLR2 and induce immune responses that can be used against Leishmania infection in a susceptible host. The binding affinity of barley β-glucan and zymosan with Dectin-1 and TLR2 was studied in silico. Barley β-glucan- and zymosan-induced dectin-1 and TLR2 co-localization was studied by confocal microscopy and co-immunoprecipitation. These ligands-induced signalling and effector functions were assessed by Western blot analyses and various immunological assays. Finally, the anti-leishmanial potential of barley β-glucan and zymosan was tested in Leishmania donovani -infected macrophages and in L. donovani-infected BALB/c mice. Both barley β-glucan and zymosan interacted with TLR2 and dectin-1, but with a much stronger binding affinity for the latter, and therefore induced co-localization of these two receptors on BALB/c-derived macrophages. Both ligandsactivated MyD88- and Syk-mediated downstream pathways for heightened inflammatory responses in L. donovani-infected macrophages. These two ligands induced T cell–dependent host protection in L. donovani-infected BALB/c mice. These results establish a novel modus operandi of β-glucans through dectin-1 and TLR2 and suggest an immuno-modulatory potential against infectious diseases.