Cutting Edge: Activation of Toll-Like Receptor 2 Induces a Th2 Immune Response and Promotes Experimental Asthma

TLDR

Recognition of microbial components by antigen‑presenting cells via Toll‑like receptors triggers adaptive immune responses. The study demonstrates that TLR2 activation by Pam3Cys, unlike TLR9 activation, drives a Th2‑skewed immune response. TLR2 stimulation with Pam3Cys induced Th2 cytokines (IL‑13, IL‑1β, GM‑CSF) with minimal Th1 cytokines, aggravated experimental asthma, and shows that TLR type determines adaptive immune polarization and may initiate Th2‑mediated disorders such as asthma.

Abstract

Abstract Recognition of microbial components by APCs and their activation through Toll-like receptors (TLR) leads to the induction of adaptive immune responses. In this study, we show that activation of TLR2 by its synthetic ligand Pam3Cys, in contrast to activation of TLR9 by immunostimulatory DNA (ISS-ODN), induces a prominent Th2-biased immune response. Activation of APCs by Pam3Cys resulted in the induction of Th2-associated effector molecules like IL-13, and IL-1β, GM-CSF and up-regulation of B7RP-1, but low levels of Th1-associated cytokines (IL-12, IFNα, IL-18, IL-27). Accordingly, TLR2 ligands aggravated experimental asthma. These data indicate that the type of TLR stimulation during the initial phase of immune activation determines the polarization of the adaptive immune response and may play a role in the initiation of Th2-mediated immune disorders, such as asthma.