Pathogen-associated molecular pattern explained

Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes, but not present in the host.[1] They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals.[2] This allows the innate immune system to recognize pathogens and thus, protect the host from infection.[3]

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)[4] or other cytokines.[5]

Common PAMPs

A vast array of different types of molecules can serve as PAMPs, including glycans and glycoconjugates.[6] Flagellin is also another PAMP that is recognized via the constant domain, D1 by TLR5.[7] Despite being a protein, its N- and C-terminal ends are highly conserved, due to its necessity for function of flagella. Nucleic acid variants normally associated with viruses, such as double-stranded RNA (dsRNA), are recognized by TLR3 and unmethylated CpG motifs are recognized by TLR9.[8] The CpG motifs must be internalized in order to be recognized by TLR9. Viral glycoproteins, as seen in the viral-envelope, as well as fungal PAMPS on the cell surface or fungi are recognized by TLR2 and TLR4.

Gram-negative bacteria

Bacterial lipopolysaccharides (LPSs), also known as endotoxins, are found on the cell membranes of gram-negative bacteria,[9] are considered to be the prototypical class of PAMPs. The lipid portion of LPS, lipid A, contains a diglycolamine backbone with multiple acyl chains. This is the conserved structural motif that is recognized by TLR4, particularly the TLR4-MD2 complex.[10] Microbes have two main strategies in which they try to avoid the immune system, either by masking lipid A or directing their LPS towards an immunomodulatory receptor.

Peptidoglycan (PG) is also found within the membrane walls of gram-negative bacteria[11] and is recognized by TLR2, which is usually in a heterodimer of with TLR1 or TLR6.[12] [13]

Gram-positive bacteria

Lipoteichoic acid (LTA) from gram-positive bacteria, bacterial lipoproteins (sBLP), a phenol soluble factor from Staphylococcus epidermidis, and a component of yeast walls called zymosan, are all recognized by a heterodimer of TLR2 and TLR1 or TLR6. However, LTAs result in a weaker pro-inflammatory response compared to lipopeptides, as they are only recognized by TLR2 instead of the heterodimer.

History

First introduced by Charles Janeway in 1989, PAMP was used to describe microbial components that would be considered foreign in a multicellular host. 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),[14] [15] [16] 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.[17] 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.[18]

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.[19] TLR2 with association of TLR1 can recognize cell wall lipoprotein antigens from Mycobacterium tuberculosis, which also induce production of cytokines by macrophages.[20] TLR9 can be activated by mycobacterial DNA.

See also

Further reading

Notes and References

  1. Tang . Daolin . Kang . Rui . Coyne . Carolyn B. . Zeh . Herbert J. . Lotze . Michael T. . September 2012 . PAMPs and DAMPs: signal 0s that spur autophagy and immunity . Immunological Reviews . en . 249 . 1 . 158–175 . 10.1111/j.1600-065X.2012.01146.x . 3662247 . 22889221.
  2. Ingle RA, Carstens M, Denby KJ . PAMP recognition and the plant-pathogen arms race . BioEssays . 28 . 9 . 880–889 . September 2006 . 16937346 . 10.1002/bies.20457 . 26861625 .
  3. Book: Review of medical microbiology and immunology . Levinson W . 2016 . 978-0-07-184574-8 . 14th . New York . 951918628.
  4. Pichlmair A, Reis e Sousa C . September 2007 . Innate recognition of viruses . Immunity . 27 . 3 . 370–383 . 10.1016/j.immuni.2007.08.012 . 17892846 . free.
  5. Akira S, Uematsu S, Takeuchi O . February 2006 . Pathogen recognition and innate immunity . Cell . 124 . 4 . 783–801 . 10.1016/j.cell.2006.02.015 . 16497588 . free.
  6. 6 . 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 . 10.1016/j.jaut.2014.12.002 . 4340844 . 25578468.
  7. Akira . Shizuo . Uematsu . Satoshi . Takeuchi . Osamu . February 2006 . Pathogen Recognition and Innate Immunity . Cell . en . 124 . 4 . 783–801 . 10.1016/j.cell.2006.02.015. 16497588 . 14357403 . free .
  8. 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 . 10.3389/fimmu.2013.00248 . 3759294 . 24032031 . free.
  9. Silhavy TJ, Kahne D, Walker S . The bacterial cell envelope . Cold Spring Harbor Perspectives in Biology . 2 . 5 . a000414 . May 2010 . 20452953 . 2857177 . 10.1101/cshperspect.a000414 .
  10. Ahmad-Nejad . Parviz . Häcker . Hans . Rutz . Mark . Bauer . Stefan . Vabulas . Ramunas M . Wagner . Hermann . June 20, 2002 . Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments . European Journal of Immunology . 32 . 7 . 1819–2094 . 10.1002/1521-4141(200207)32:7<1958::AID-IMMU1958>3.0.CO;2-U . 12115616 . 31631310 . free .
  11. Silhavy . Thomas J. . Kahne . Daniel . Walker . Suzanne . May 2010 . The bacterial cell envelope . Cold Spring Harbor Perspectives in Biology . 2 . 5 . a000414 . 10.1101/cshperspect.a000414 . 1943-0264 . 2857177 . 20452953.
  12. 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 . 107–115 . 10.1016/j.jim.2013.08.004 . 23954282.
  13. Janeway . Charles A. . Medzhitov . Ruslan . April 2002 . Innate Immune Recognition . Annual Review of Immunology . en . 20 . 1 . 197–216 . 10.1146/annurev.immunol.20.083001.084359 . 11861602 . 39036433 . 0732-0582.
  14. Koropatnick TA, Engle JT, Apicella MA, Stabb EV, Goldman WE, McFall-Ngai MJ . Microbial factor-mediated development in a host-bacterial mutualism . Science . 306 . 5699 . 1186–1188 . November 2004 . 15539604 . 10.1126/science.1102218 . 41603462 . 2004Sci...306.1186K .
  15. Ausubel FM . Are innate immune signaling pathways in plants and animals conserved? . Nature Immunology . 6 . 10 . 973–979 . October 2005 . 16177805 . 10.1038/ni1253 . 7451505 .
  16. Didierlaurent A, Simonet M, Sirard JC . Innate and acquired plasticity of the intestinal immune system . Cellular and Molecular Life Sciences . 62 . 12 . 1285–1287 . June 2005 . 15971103 . 1865479 . 10.1007/s00018-005-5032-4 .
  17. Rumbo M, Nempont C, Kraehenbuhl JP, Sirard JC . Mucosal interplay among commensal and pathogenic bacteria: lessons from flagellin and Toll-like receptor 5 . FEBS Letters . 580 . 12 . 2976–2984 . May 2006 . 16650409 . 10.1016/j.febslet.2006.04.036 . 14300007 . 10.1.1.320.8479 . (Free full text available)
  18. Jones JD, Dangl JL . The plant immune system . Nature . 444 . 7117 . 323–329 . November 2006 . 17108957 . 10.1038/nature05286 . free . 2006Natur.444..323J .
  19. Quesniaux V, Fremond C, Jacobs M, Parida S, Nicolle D, Yeremeev V, Bihl F, Erard F, Botha T, Drennan M, Soler MN, Le Bert M, Schnyder B, Ryffel B . 6 . Toll-like receptor pathways in the immune responses to mycobacteria . Microbes and Infection . 6 . 10 . 946–959 . August 2004 . 15310472 . 10.1016/j.micinf.2004.04.016 . free .
  20. Thoma-Uszynski S, Stenger S, Takeuchi O, Ochoa MT, Engele M, Sieling PA, Barnes PF, Rollinghoff M, Bolcskei PL, Wagner M, Akira S, Norgard MV, Belisle JT, Godowski PJ, Bloom BR, Modlin RL . 6 . Induction of direct antimicrobial activity through mammalian toll-like receptors . Science . 291 . 5508 . 1544–1547 . February 2001 . 11222859 . 10.1126/science.291.5508.1544 . 2001Sci...291.1544T .

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