Toll-like receptor 2 signalling: Significance in megakaryocyte development through wnt signalling cross-talk and cytokine induction

Abstract

TLR2 is a toll-like receptor protein which is involved in innate immune responses. TLR2 recognize several virus, fungal and bacterial pathogens, upon their uptake cause internalization and cellular activation. During this process several cytokines participate including interleukins, IL6 and IL12. Interestingly, TLR2 is expressed on megakaryocytes (MKs) and platelets, which is crucial for immune mediated platelet activation. The role of TLR2 on MKs is not completely understood. We observed TLR2 induction leads to MK maturation and is involved in production of ROS which is essential for MK development. In Dami cells, TLR2 up-regulation causes increase in the cytokine production, particularly IL-6, which has been shown to stimulate CFU formation and CD41 expression. Additionally, TLR2 ligand induces wnt β-catenin signalling pathway components suggesting a cross talk between wnt and TLR pathway leading to maturation of MKs. This study shows TLR2 signalling induce cytokine production and regulate wnt signalling thereby cause maturation of MKs.