Pattern Recognition Receptors (PRRs)

Pattern Recognition Receptors (PRRs) are innate immune receptors that recognizes PAMPs (pathogen-associated molecular patterns) / Microbial associated molecular patterns (MAMPs) and induces PAMP-triggered immunity (PTI) (1). Also endogenous intracellular molecules released by dying cells (Damage Associated Molecular Pattern Molecules (DAMPs)), initiate Inflammation (3). They were initially described as sensors for "danger signals" from pathogens (e.g., viral DNA, bacterial proteins, ...) (13, 14, 15, 16, 17, 18, 19, 20, 21, 22). Ligands for PRRs are not exclusive to pathogens, and are abundantly produced by the resident microbiota during normal colonization (23).

The first step of the interaction between the gut microbiota and host cells via PAMPs (pathogen-associated molecular patterns (?id=29fe6141-9cd3-4cf0-bcf6-5c1c87d720d5&linkText=PAMPs+%28pathogen-associated+molecular+patterns)) / Microbial associated molecular patterns (MAMPs) (?id=4a4886e7-c771-4232-bcae-f3e98b7aa66e&linkText=Microbial+associated+molecular+patterns+%28MAMPs%29)is mediated by pattern recognition receptors (PRRs), which sense microorganisms through conserved molecular structures. Once the microbial signatures are recognized by the host, usually a transcriptional response (e.g., NFKB) follows, which determines the outcome of this interaction and is critical for maintaining the balance between homeostasis and inflammation (2).

The innate immune system uses pattern recognition receptors (PRRs) to detect pathogens (acting as pathogen sensors) and maintain homeostasis. PRRs include membrane-bound receptors like Toll-like receptors (TLRs) and cytosolic receptors like nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). Different classes of PRRs recognize microbial components called pathogen-associated molecular patterns (PAMPs) and host-derived damage-associated molecular patterns (DAMPs). PRR sensing activates innate immune signaling pathways, leading to the production of cytokines and chemokines. However, excessive activation can cause inflammation and disease, so PRR sensing and immune activation must be tightly controlled (4, 5, 6, 7, 8, 9, 10, 11, 25). Both positive and negative interactions between Toll-Like Receptors (TLRs) and NOD-like receptors (NLRs) potentially exist to modulate inflammatory and immunoregulatory cytokine responses (26).

Host PRRs are important regulators of Cardiovascular Diseases (CVD) pathogenesis (12)

PRRs required for ICD (immunogenic cell death) (24)

References:

(1) Pradeu et al. 2024 Immunity 57(4): 613-631
(2) Zhang et al. 2022g Front. Cell Dev. Biol. 10: 874940
(3) Priem et al. 2020 Trends in Immunology 41: 421
(4) Janeway Jr. 1989 Cold Spring Harb. Symp. Quant. Biol. 54: 1-13
(5) Matzinger 1994 Annu. Rev. Immunol. 12: 991-1045
(6) Medzhitov & Janeway Jr. 1997
(7) Akira et al. 2006 Cell 124: 783–801
(8) Kanneganti et al. 2007 Immunity 27: 549-559
(9) Kumar et al. 2011 Int. Rev. Immunol. 30: 16-34
(10) Gong et al. 2020 Nat. Rev. Immunol. 20: 95-112
(11) Kanneganti 2020 Immunol. Rev. 297: 5-12
(12) Brown & Hazen 2018 Nat. Rev. Microbiol. 16: 171-181
(13) Shekarian et al. 2017 Ann Oncol. 28(8): 1756-1766
(14) Matzinger 2002 Science 296: 301-305
(15) Chen & Nunez 2010 Nat Rev Immunol. 10:826–837
(16) Galluzzi et al. 2012 Nat Rev Mol Cell Biol. 13:780–788
(17) Brenner et al. 2013 J Hepatol. 59: 583–594
(18) Fucikova et al. 2015 Front Immunol. 6: 402
(19) Garg et al. 2015 Front Immunol. 6: 588
(20) Vacchelli et al. 2016 Oncoimmunology. 5: e1118600
(21) Galluzzi et al. 2017
(22) Garg et al. 2017a Oncoimmunology. 6: e1386829
(23) Chu & Mazmanian 2013
(24) Krysko et al., 2012
(25) Mills 2011
(26) Hill & Artis 2010

see also:
Innate immune receptors