An Overview of Pathogen Recognition Receptors for Innate Immunity in Dental Pulp

Abstract

Pathogen recognition receptors (PRRs) are a class of germ line-encoded receptors that recognize pathogen-associated molecular patterns (PAMPs). The activation of PRRs is crucial for the initiation of innate immunity, which plays a key role in first-line defense until more specific adaptive immunity is developed. PRRs differ in the signaling cascades and host responses activated by their engagement and in their tissue distribution. Currently identified PRR families are the Toll-like receptors (TLRs), the C-type lectin receptors (CLRs), the nucleotide-binding oligomerization domain-like receptors (NLRs), the retinoic acid-inducible gene-I-like receptors (RLRs), and the AIM2-like receptor (ALR). The environment of the dental pulp is substantially different from that of other tissues of the body. Dental pulp resides in a low compliance root canal system that limits the expansion of pulpal tissues during inflammatory processes. An understanding of the PRRs in dental pulp is important for immunomodulation and hence for developing therapeutic targets in the field of endodontics. Here we comprehensively review recent finding on the PRRs and the mechanisms by which innate immunity is activated. We focus on the PRRs expressed on dental pulp and periapical tissues and their role in dental pulp inflammation.

Figure 1

Schematic overview of TLR and NLR signaling pathways. PAMPs and DAMPs are recognized by PRRs. Heterodimer of TLR1/6+TLR2, TLR4, and endosomal TLR3 activate TRIF pathway, followed by induction of IRF and NF-κB. TLR5 and endosomal TLR9 and TLR7 activate MyD88 pathway, followed by activation of MAPK, NF-κB, and IRF7. NOD1 and NOD2 are cytoplasmic PRRs, and they trigger NF-κB, and NALP3 inflammasome recruits and activates caspase-1 pathway. DAMP: damage-associated molecular patterns; IRF: IFN-regulatory factor; MAPK; mitogen-activated protein kinase; MyD88; myeloid differentiation primary-response gene 88; NF-κB: nuclear factor-κB; NALP3: NACHT, LRR, and pyrin domain containing protein 3; NOD: nucleotide-binding oligomerization domain; NLR: NOD-like receptor; PAMP: pathogen-associated molecular patterns; TLR: Toll-like receptor; TRIF: Toll/IL-1R (TIR) domain containing adaptor protein inducing IFN-β.