Pattern Recognition Beyond the Surface: Soluble Pattern Recognition and Their Role in Periodontitis

Sivaraman Prakasam, Justin Merritt, Jens Kreth

Research output: Contribution to journalReview articlepeer-review


Purpose of Review: Pattern recognition receptors (PRRs) are important mediators of tissue homeostasis. Soluble forms of PRRs, including a novel group of molecules called peptidoglycan recognition proteins (PGRPs) have very important regulatory roles. However, they remain poorly understood compared to other forms of PRRs, particularly in the context of periodontitis. In this review, we discuss the different types of soluble PRRs, their functions, and the limited knowledge available about their regulation during periodontitis. We introduce PGRPs and the emerging data on their expression during periodontitis. Recent Findings: Interest in soluble PRRs continues to grow due to their tremendous value in diagnostic and therapeutic application. Specific mechanisms of how soluble PRRs are generated have now been identified including alternative spicing, ectodomain shedding, and diffusion from membrane PRRs. Proteins that have PRR functions but no corresponding membrane PRR have also been identified. They are collectively termed as pattern recognition molecules (PRMs). PGRPs are the newest members of these human PRM. Four isoforms of PGRP, namely, PGRP1, PGRP2, PGRP3, and PGRP4, have been identified. Consensus is emerging that PRMs are generally elevated in serum, gingival crevicular fluid, and saliva during periodontitis, and the levels of PRMs reduce with non-surgical therapy. However, the relationship between periodontitis and levels of soluble isoforms of membrane-bound PRRs is much more complex. Conflicting reports have emerged on the levels of these proteins during periodontitis. Similarly, very few studies have examined the function and regulation of sPRRs in periodontitis. Limited available evidence suggests that PGRP1 may be a key regulator of gingival inflammation. However, not much is known about other isoforms of PGRPs. Recently, we reported increased levels of PGRP3 and PGPR4 in gingiva and saliva during periodontitis, suggesting an important but unknown regulation of these proteins in the periodontium. Summary: Soluble PRRs, particularly PGRPs, have a contextual divalent function. They maintain homeostasis via mechanisms that dampen tissue inflammation. Contextually, they also aid in activating inflammation and antigen presentation. Understanding the function and regulation of soluble PRRs is vital for development of novel biologically mediated periodontal therapies and point of care diagnostics.

Original languageEnglish (US)
Pages (from-to)185-196
Number of pages12
JournalCurrent Oral Health Reports
Issue number4
StatePublished - Dec 2022


  • Innate immunity
  • Pattern recognition molecules
  • Peptidoglycan recognition proteins
  • Periodontitis
  • Saliva
  • Soluble pattern recognition receptors

ASJC Scopus subject areas

  • Surgery
  • Oral Surgery
  • Immunology and Microbiology (miscellaneous)


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