Research progress on Toll-like receptor signal transduction and its roles in antimicrobial immune responses

Abstract

When microorganisms invade a host, the innate immune system first recognizes the pathogen-associated molecular patterns of these microorganisms through pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are known transmembrane PRRs existing in both invertebrates and vertebrates. Upon ligand recognition, TLRs initiate a cascade of signaling events; promote the pro-inflammatory cytokine, type I interferon, and chemokine expression; and play an essential role in the modulation of the host’s innate and adaptive immunity. Therefore, it is of great significance to improve our understanding of antimicrobial immune responses by studying the role of TLRs and their signal molecules in the host’s defense against invading microbes. This paper aims to summarize the specificity of TLRs in recognition of conserved microbial components, such as lipoprotein, lipopolysaccharide, flagella, endosomal nucleic acids, and other bioactive metabolites derived from microbes. This set of interactions helps to elucidate the immunomodulatory effect of TLRs and the signal transduction changes involved in the infectious process and provide a novel therapeutic strategy to combat microbial infections.

Bacterial Ghosts-Based Vaccine and Drug Delivery Systems

“…The MyD88-dependent intracellular signaling pathway involves activation of the NF-κBmediated inflammatory factor gene expression (TNF-α, IL-1,6,8, etc.) and activation of the MAPK pathway (including JNK and P38 pathways) [62,63]. The MyD88-independent pathway (TRIF dependent signaling pathways) induces the expressions of transcription factor IRF3, resulting in expressions of type I interferon (IFN-1) and activation of NF-κB to promote the expressions of inflammatory factors.…”

Glucocorticoid-Induced Leucine Zipper-Mediated TLR2 Downregulation Accounts for Reduced Neutrophil Activity Following Acute DEX Treatment

“…In particular, both few and controversial studies are available regarding glucocorticoid-mediated regulation of the cellular components of neutrophils, such as Toll-like receptor 2 (TLR2). TLR2 belongs to a family of type I transmembrane proteins expressed on the surface of several immune cells that recognize a wide range of pathogen-associated molecular patterns (PAMPs) [ 23 , 24 ]. Once activated, TLRs initiate intra-signalling pathways that ultimately lead to the transcriptional regulation of pro-inflammatory genes, including cytokines (e.g., type I IFNs) [ 25 , 26 , 27 , 28 ].…”

Extracellular DNA (eDNA). A Major Ubiquitous Element of the Bacterial Biofilm Architecture

“…However, whether TLR9 plays a protective or deleterious role in host defense against P. aeruginosa remained to be determined. TLR9 plays an essential role in activating innate immunity by recognizing CpG specific motifs present in microbial DNA [10,140]. It is however reported that TLR9 down-regulates the innate immune response against P. aeruginosa and that the absence of TLR9 leads to an early increase in the inflammatory response [141].…”