Pathogen-associated molecular pattern

Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. A vast array of different types of molecules can serve as PAMPs, including glycans and glycoconjugates.[1]

PAMPs activate innate immune responses, protecting the host from infection, by identifying some conserved nonself molecules. Bacterial lipopolysaccharides (LPSs), endotoxins found on the cell membranes of gram-negative bacteria,[2] are considered to be the prototypical class of PAMPs. LPSs are specifically recognised by TLR4, a recognition receptor of the innate immune system. Other PAMPs include bacterial flagellin (recognized by TLR5), lipoteichoic acid from gram-positive bacteria (recognized by TLR2),[3] peptidoglycan (recognized by TLR2),[3] and nucleic acid variants normally associated with viruses, such as double-stranded RNA (dsRNA), recognized by TLR3 or unmethylated CpG motifs, recognized by TLR9.[4] Although the term "PAMP" is relatively new, the concept that molecules derived from microbes must be detected by receptors from multicellular organisms has been held for many decades, and references to an "endotoxin receptor" are found in much of the older literature. The recognition of PAMPs by the PRRs triggers activation of several signaling cascades in the host immune cells like the stimulation of interferons (IFNs)[5] or other cytokines.[6]

PAMP

The term "PAMP" has been criticized on the grounds that most microbes, not only pathogens, express the molecules detected; the term microbe-associated molecular pattern (MAMP),[7][8][9] has therefore been proposed. A virulence signal capable of binding to a pathogen receptor, in combination with a MAMP, has been proposed as one way to constitute a (pathogen-specific) PAMP.[10] Plant immunology frequently treats the terms "PAMP" and "MAMP" interchangeably, considering their recognition to be the first step in plant immunity, PTI (PAMP-triggered immunity), a relatively weak immune response that occurs when the host plant does not also recognize pathogenic effectors that damage it or modulate its immune response.[11]

In mycobacteria

Mycobacteria are intracellular bacteria which survive in host macrophages. The mycobacterial wall is composed of lipids and polysaccharides and also contains high amounts of mycolic acid. Purified cell wall components of mycobacteria activate mainly TLR2 and also TLR4. Lipomannan and lipoarabinomannan are strong immunomodulatory lipoglycans.[12] TLR2 with association of TLR1 can recognize cell wall lipoprotein antigens from Mycobacterium tuberculosis, which also induce production of cytokines by macrophages.[13] TLR9 can be activated by mycobacterial DNA.

See also
  • DAMP
  • Tissue remodeling

Notes and references
  1. Maverakis E, Kim K, Shimoda M, Gershwin ME, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB (February 2015). "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review". Journal of Autoimmunity. 57 (6): 1–13. doi:10.1016/j.jaut.2014.12.002. PMC 4340844. PMID 25578468.
  2. Silhavy TJ, Kahne D, Walker S (May 2010). "The bacterial cell envelope". Cold Spring Harbor Perspectives in Biology. 2 (5): a000414. doi:10.1101/cshperspect.a000414. PMC 2857177. PMID 20452953.
  3. Dammermann W, Wollenberg L, Bentzien F, Lohse A, Lüth S (October 2013). "Toll like receptor 2 agonists lipoteichoic acid and peptidoglycan are able to enhance antigen specific IFNγ release in whole blood during recall antigen responses". Journal of Immunological Methods. 396 (1–2): 107–15. doi:10.1016/j.jim.2013.08.004. PMID 23954282.
  4. Mahla RS, Reddy MC, Prasad DV, Kumar H (September 2013). "Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology". Frontiers in Immunology. 4: 248. doi:10.3389/fimmu.2013.00248. PMC 3759294. PMID 24032031.
  5. Pichlmair, Andreas; Reis e Sousa, Caetano (September 2007). "Innate Recognition of Viruses". Immunity. 27 (3): 370–383. doi:10.1016/j.immuni.2007.08.012. PMID 17892846.
  6. Akira, Shizuo; Uematsu, Satoshi; Takeuchi, Osamu (February 2006). "Pathogen Recognition and Innate Immunity". Cell. 124 (4): 783–801. doi:10.1016/j.cell.2006.02.015. PMID 16497588.
  7. Koropatnick, Tanya A.; Engle, Jacquelyn T.; Apicella, Michael A.; Stabb, Eric V.; Goldman, William E.; McFall-Ngai, Margaret J. (2004-11-12). "Microbial factor-mediated development in a host-bacterial mutualism". Science. 306 (5699): 1186–1188. Bibcode:2004Sci...306.1186K. doi:10.1126/science.1102218. ISSN 1095-9203. PMID 15539604. S2CID 41603462.
  8. Ausubel FM (October 2005). "Are innate immune signaling pathways in plants and animals conserved?". Nature Immunology. 6 (10): 973–9. doi:10.1038/ni1253. PMID 16177805. S2CID 7451505.
  9. Didierlaurent A, Simonet M, Sirard JC (June 2005). "Innate and acquired plasticity of the intestinal immune system". Cellular and Molecular Life Sciences. 62 (12): 1285–7. doi:10.1007/s00018-005-5032-4. PMC 1865479. PMID 15971103.
  10. Rumbo M, Nempont C, Kraehenbuhl JP, Sirard JC (May 2006). "Mucosal interplay among commensal and pathogenic bacteria: lessons from flagellin and Toll-like receptor 5". FEBS Letters. 580 (12): 2976–84. CiteSeerX 10.1.1.320.8479. doi:10.1016/j.febslet.2006.04.036. PMID 16650409. S2CID 14300007. (Free full text available)
  11. Jones JD, Dangl JL (November 2006). "The plant immune system". Nature. 444 (7117): 323–9. Bibcode:2006Natur.444..323J. doi:10.1038/nature05286. PMID 17108957.
  12. Quesniaux, Valerie; Fremond, Cecile; Jacobs, Muazzam; Parida, Shreemanta; Nicolle, Delphine; Yeremeev, Vladimir; Bihl, Franck; Erard, Francois; Botha, Tania; Drennan, Michael; Soler, Marie-Noelle; Le Bert, Marc; Schnyder, Bruno; Ryffel, Bernhard (August 2004). "Toll-like receptor pathways in the immune responses to mycobacteria". Microbes and Infection. 6 (10): 946–959. doi:10.1016/j.micinf.2004.04.016. PMID 15310472.
  13. Thoma-Uszynski, S. (23 February 2001). "Induction of Direct Antimicrobial Activity Through Mammalian Toll-Like Receptors". Science. 291 (5508): 1544–1547. Bibcode:2001Sci...291.1544T. doi:10.1126/science.291.5508.1544. PMID 11222859.
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