Function and Phenotype of Microglia Are Determined by Toll-Like Receptor 2/Toll-Like Receptor 4 Activation Sequence

Abstract

Toll-like receptors (TLRs) initiate and maintain host defenses. These receptors play important roles in innate immunity and in various diseases. Different TLRs bind to diverse ligands that trigger distinct protein expression patterns. Few studies have focused on the interaction between different TLRs. We found that TLR2 priming downregulates TLR4 transcription, and expression of TLR4 activation induced major histocompatibility complex II (MHC II), adhesion molecule intercellular adhesion molecule-1 (ICAM-1), phagocytosis marker CD11b/CD18, and Fcgamma receptor (FcgammaR) expression. In contrast, TLR4 priming increases TLR2 transcription and expression. In addition, TLR4 priming increases secretion of certain proinflammatory mediators. Expression of costimulatory molecules CD80/CD86 increases with TLR2 or TLR4 activation sequences. Our results reveal that TLR2/TLR4 activation may determine disease pathogenesis and prognosis.