PRR Function of Innate Immune Receptors in Recognition of Bacteria or Bacterial Ligands

  • Aakanksha Gulati
  • Deepinder Kaur
  • G. V. R. Krishna Prasad
  • Arunika MukhopadhayaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1112)


Recognition of a bacterial attack is the first and the most important step in clearing the bacteria from the body of the host. Towards this, the host innate immune system employs pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), nucleotide-binding leucine-rich repeat-containing receptors (NLRs) and scavenger receptors (SRs) present mostly in innate immune cells. These receptors sense the presence of bacteria and help in spreading the signal to the host, which results in recruitment of other immune cells leading to the elimination of the bacteria from the system. Since their discovery, a lot has been established about these receptors. Their role has been elucidated not only in pathogen recognition but also in eradication of the dead cells from the system. This review is focussed mainly on their role in the bacterial recognition and how these receptors play a role in eliciting an immune response against bacteria in the host.


Pattern recognition receptor TLR NLR Scavenger receptor Innate immunity 


  1. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511 doi:10.1038/nri1391nri1391[pii]PubMedPubMedCentralCrossRefGoogle Scholar
  2. Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2:675–680 doi:10.1038/9060990609[pii]PubMedCrossRefGoogle Scholar
  3. Allen IC et al (2010) The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med 207:1045–1056 doi:jem.20100050 [pii]10.1084/jem.20100050PubMedPubMedCentralCrossRefGoogle Scholar
  4. Armant MA, Fenton MJ (2002) Toll-like receptors: a family of pattern-recognition receptors in mammals. Genome Biol 3:REVIEWS3011PubMedPubMedCentralCrossRefGoogle Scholar
  5. Arredouani MS (2014) Is the scavenger receptor MARCO a new immune checkpoint? Oncoimmunology 3:e955709. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Baccala R, Hoebe K, Kono DH, Beutler B, Theofilopoulos AN (2007) TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity. Nat Med 13:543–551 doi:nm1590 [pii]10.1038/nm1590PubMedCrossRefGoogle Scholar
  7. Baranova IN et al (2008) Role of human CD36 in bacterial recognition, phagocytosis, and pathogen-induced JNK-mediated signaling. J Immunol 181:7147–7156PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bauernfeind FG et al (2009) Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol 183:787–791 doi:jimmunol.0901363 [pii]10.4049/jimmunol.0901363PubMedPubMedCentralCrossRefGoogle Scholar
  9. Ben J, Zhu X, Zhang H, Chen Q (2015) Class A1 scavenger receptors in cardiovascular diseases. Br J Pharmacol 172:5523–5530 doi:10.1111/bph.13105PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bertheloot D et al (2016) RAGE enhances TLR responses through binding and internalization of RNA. J Immunol 197:4118–4126 doi:10.4049/jimmunol.1502169PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bertrand MJ, Doiron K, Labbe K, Korneluk RG, Barker PA, Saleh M (2009) Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2. Immunity 30:789–801 doi:S1074-7613(09)00203-9 [pii]10.1016/j.immuni.2009.04.011PubMedCrossRefGoogle Scholar
  12. Beutler BA (2009) TLRs and innate immunity. Blood 113:1399–1407 doi:blood-2008-07-019307 [pii]10.1182/blood-2008-07-019307PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bierhaus A et al (2001) Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes 50:2792–2808PubMedCrossRefGoogle Scholar
  14. Bowdish DM et al (2009) MARCO, TLR2, and CD14 are required for macrophage cytokine responses to mycobacterial trehalose dimycolate and Mycobacterium tuberculosis. PLoS Pathog 5:e1000474. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Broz P, von Moltke J, Jones JW, Vance RE, Monack DM (2010) Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing. Cell Host Microbe 8:471–483 doi:S1931-3128(10)00380-X [pii]10.1016/j.chom.2010.11.007PubMedPubMedCentralCrossRefGoogle Scholar
  16. Canton J, Neculai D, Grinstein S (2013) Scavenger receptors in homeostasis and immunity. Nat Rev Immunol 13:621–634. CrossRefPubMedGoogle Scholar
  17. Cao D, Luo J, Chen D, Xu H, Shi H, Jing X, Zang W (2016) CD36 regulates lipopolysaccharide-induced signaling pathways and mediates the internalization of Escherichia coli in cooperation with TLR4 in goat mammary gland epithelial cells. Sci Rep 6:23132. CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cervantes JL, Weinerman B, Basole C, Salazar JC (2012) TLR8: the forgotten relative revindicated. Cell Mol Immunol 9:434–438 doi:cmi201238 [pii]10.1038/cmi.2012.38PubMedPubMedCentralCrossRefGoogle Scholar
  19. Chen ZJ (2005) Ubiquitin signalling in the NF-kappaB pathway. Nat Cell Biol 7:758–765 doi:ncb0805-758 [pii]10.1038/ncb0805-758PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chuong C, Katz J, Pauley KM, Bulosan M, Cha S (2009) RAGE expression and NF-kappaB activation attenuated by extracellular domain of RAGE in human salivary gland cell line. J Cell Physiol 221:430–434. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Coller SP, Paulnock DM (2001) Signaling pathways initiated in macrophages after engagement of type A scavenger receptors. J Leukocyte Biol 70:142–148PubMedGoogle Scholar
  22. Delneste Y et al (2002) Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity 17:353–362PubMedCrossRefGoogle Scholar
  23. Demaria O et al (2010) TLR8 deficiency leads to autoimmunity in mice. J Clin Invest 120:3651–3662 doi:42081 [pii]10.1172/JCI42081PubMedPubMedCentralGoogle Scholar
  24. Dostert C, Petrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J (2008) Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320:674–677 doi:1156995 [pii]10.1126/science.1156995PubMedPubMedCentralCrossRefGoogle Scholar
  25. Doyle SE et al (2004) Toll-like receptors induce a phagocytic gene program through p38. J Exp Med 199:81–90. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Duewell P et al (2010) NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357–1361 doi:nature08938 [pii]10.1038/nature08938PubMedPubMedCentralCrossRefGoogle Scholar
  27. Duncan JA et al (2009) Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome. J Immunol 182:6460–6469 doi:182/10/6460 [pii]10.4049/jimmunol.0802696PubMedPubMedCentralCrossRefGoogle Scholar
  28. Dupaul-Chicoine J et al (2010) Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. Immunity 32:367–378 doi:S1074-7613(10)00082-8 [pii]10.1016/j.immuni.2010.02.012PubMedCrossRefGoogle Scholar
  29. Etzerodt A, Moestrup SK (2013) CD163 and inflammation: biological, diagnostic, and therapeutic aspects. Antioxid Redox Signal 18:2352–2363. CrossRefPubMedPubMedCentralGoogle Scholar
  30. Eugenin J, Vecchiola A, Murgas P, Arroyo P, Cornejo F, von Bernhardi R (2016) Expression pattern of scavenger receptors and amyloid-beta phagocytosis of astrocytes and microglia in culture are modified by acidosis: implications for Alzheimer’s disease. J Alzheimer’s Dis: JAD 53:857–873. CrossRefGoogle Scholar
  31. Fabriek BO et al (2009) The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria. Blood 113:887–892. CrossRefPubMedGoogle Scholar
  32. Faustin B et al (2007) Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol Cell 25:713–724 doi:S1097-2765(07)00078-0 [pii]10.1016/j.molcel.2007.01.032PubMedCrossRefGoogle Scholar
  33. Fernandes-Alnemri T et al (2010) The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat Immunol 11:385–393 doi:ni.1859 [pii]10.1038/ni.1859PubMedPubMedCentralCrossRefGoogle Scholar
  34. Ferwerda G et al (2005) NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis. PLoS Pathog 1:279–285. CrossRefPubMedGoogle Scholar
  35. Finger JN et al (2012) Autolytic proteolysis within the function to find domain (FIIND) is required for NLRP1 inflammasome activity. J Biol Chem 287:25030–25037 doi:M112.378323 [pii]10.1074/jbc.M112.378323PubMedPubMedCentralCrossRefGoogle Scholar
  36. Fitzgerald ML, Moore KJ, Freeman MW, Reed GL (2000) Lipopolysaccharide induces scavenger receptor A expression in mouse macrophages: a divergent response relative to human THP-1 monocyte/macrophages. J Immunol 164:2692–2700PubMedCrossRefGoogle Scholar
  37. Franchi L, Eigenbrod T, Munoz-Planillo R, Nunez G (2009) The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol 10:241–247 doi:ni.1703 [pii]10.1038/ni.1703PubMedPubMedCentralCrossRefGoogle Scholar
  38. Frew BC, Joag VR, Mogridge J (2012) Proteolytic processing of Nlrp1b is required for inflammasome activity. PLoS Pathog 8:e1002659 doi:10.1371/journal.ppat.1002659PPATHOGENS-D-11-02650[pii]PubMedPubMedCentralCrossRefGoogle Scholar
  39. Fukazawa A, Alonso C, Kurachi K, Gupta S, Lesser CF, McCormick BA, Reinecker HC (2008) GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. PLoS Pathog 4:e1000228. CrossRefPubMedPubMedCentralGoogle Scholar
  40. Furrie E, Macfarlane S, Thomson G, Macfarlane GT (2005) Toll-like receptors-2, -3 and -4 expression patterns on human colon and their regulation by mucosal-associated bacteria. Immunology 115:565–574 doi:IMM2200 [pii]10.1111/j.1365-2567.2005.02200.xPubMedPubMedCentralCrossRefGoogle Scholar
  41. Girardin SE et al (2003) Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science 300:1584–1587. CrossRefPubMedGoogle Scholar
  42. Goldin A, Beckman JA, Schmidt AM, Creager MA (2006) Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114:597–605. CrossRefPubMedGoogle Scholar
  43. Gomariz RP, Gutierrez-Canas I, Arranz A, Carrion M, Juarranz Y, Leceta J, Martinez C (2010) Peptides targeting Toll-like receptor signalling pathways for novel immune therapeutics. Curr Pharm Des 16:1063–1080 doi:BSP/CPD/E-Pub/00010[pii]PubMedCrossRefGoogle Scholar
  44. Gorden KB et al (2005) Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8. J Immunol 174:1259–1268 doi:174/3/1259[pii]PubMedCrossRefGoogle Scholar
  45. Granucci F, Petralia F, Urbano M, Citterio S, Di Tota F, Santambrogio L, Ricciardi-Castagnoli P (2003) The scavenger receptor MARCO mediates cytoskeleton rearrangements in dendritic cells and microglia. Blood 102:2940–2947. CrossRefPubMedGoogle Scholar
  46. Grimes CL, Ariyananda Lde Z, Melnyk JE, O’Shea EK (2012) The innate immune protein Nod2 binds directly to MDP, a bacterial cell wall fragment. J Am Chem Soc 134:13535–13537. CrossRefPubMedPubMedCentralGoogle Scholar
  47. Gursel M, Gursel I, Mostowski HS, Klinman DM (2006) CXCL16 influences the nature and specificity of CpG-induced immune activation. J Immunol 177:1575–1580PubMedCrossRefGoogle Scholar
  48. Hajjar AM, Ernst RK, Tsai JH, Wilson CB, Miller SI (2002) Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nat Immunol 3:354–359 doi:10.1038/ni777ni777[pii]PubMedCrossRefGoogle Scholar
  49. Hasegawa M et al (2006) Differential release and distribution of Nod1 and Nod2 immunostimulatory molecules among bacterial species and environments. J Biol Chem 281:29054–29063 doi:M602638200 [pii]10.1074/jbc.M602638200PubMedCrossRefGoogle Scholar
  50. Hendrickx DA, Koning N, Schuurman KG, van Strien ME, van Eden CG, Hamann J, Huitinga I (2013) Selective upregulation of scavenger receptors in and around demyelinating areas in multiple sclerosis. J Neuropathol Exp Neurol 72:106–118. CrossRefPubMedGoogle Scholar
  51. Hennessy EJ, Parker AE, O’Neill LA (2010) Targeting Toll-like receptors: emerging therapeutics? Nat Rev Drug Discov 9:293–307. CrossRefPubMedGoogle Scholar
  52. Hoebe K et al (2005) CD36 is a sensor of diacylglycerides. Nature 433:523–527. CrossRefPubMedGoogle Scholar
  53. Hoffmann A, Baltimore D (2006) Circuitry of nuclear factor kappaB signaling. Immunol Rev 210:171–186 doi:IMR375 [pii]10.1111/j.0105-2896.2006.00375.xPubMedCrossRefGoogle Scholar
  54. Hornef MW, Frisan T, Vandewalle A, Normark S, Richter-Dahlfors A (2002) Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J Exp Med 195:559–570PubMedPubMedCentralCrossRefGoogle Scholar
  55. Hsu HY, Hajjar DP, Khan KM, Falcone DJ (1998) Ligand binding to macrophage scavenger receptor-A induces urokinase-type plasminogen activator expression by a protein kinase-dependent signaling pathway. J Biol Chem 273:1240–1246PubMedCrossRefGoogle Scholar
  56. Hsu HY, Chiu SL, Wen MH, Chen KY, Hua KF (2001) Ligands of macrophage scavenger receptor induce cytokine expression via differential modulation of protein kinase signaling pathways. J Biol Chem 276:28719–28730. CrossRefPubMedGoogle Scholar
  57. Hsu YM et al (2007) The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat Immunol 8:198–205 doi:ni1426 [pii]10.1038/ni1426PubMedCrossRefGoogle Scholar
  58. Hsu LC et al (2008) A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U S A 105:7803–7808 doi:0802726105 [pii]10.1073/pnas.0802726105PubMedPubMedCentralCrossRefGoogle Scholar
  59. Huysamen C, Brown GD (2009) The fungal pattern recognition receptor, Dectin-1, and the associated cluster of C-type lectin-like receptors. FEMS Microbiol Lett 290:121–128. CrossRefPubMedGoogle Scholar
  60. Ibrahim ZA, Armour CL, Phipps S, Sukkar MB (2013) RAGE and TLRs: relatives, friends or neighbours? Mol Immunol 56:739–744. CrossRefPubMedGoogle Scholar
  61. Imler JL, Hoffmann JA (2001) Toll receptors in innate immunity. Trends Cell Biol 11:304–311PubMedCrossRefGoogle Scholar
  62. Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987–995 doi:10.1038/ni1112ni1112[pii]PubMedPubMedCentralCrossRefGoogle Scholar
  63. Jack CS et al (2005) TLR signaling tailors innate immune responses in human microglia and astrocytes. J Immunol 175:4320–4330 doi:175/7/4320[pii]PubMedCrossRefGoogle Scholar
  64. Jeannin P et al (2005) Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors. Immunity 22:551–560. CrossRefPubMedGoogle Scholar
  65. Jing J et al (2013) Role of macrophage receptor with collagenous structure in innate immune tolerance. J Immunol 190:6360–6367. CrossRefPubMedPubMedCentralGoogle Scholar
  66. Kawai T, Akira S (2006) TLR signaling. Cell Death Differ 13:816–825 doi:4401850[pii]10.1038/sj.cdd.4401850PubMedCrossRefGoogle Scholar
  67. Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunol 11:373–384. CrossRefGoogle Scholar
  68. Kawai T et al (2001) Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J Immunol 167:5887–5894PubMedCrossRefGoogle Scholar
  69. Keestra AM et al (2013) Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1. Nature 496:233–237 doi:nature12025 [pii]10.1038/nature12025PubMedPubMedCentralCrossRefGoogle Scholar
  70. Kierdorf K, Fritz G (2013) RAGE regulation and signaling in inflammation and beyond. J Leukocyte Biol 94:55–68. CrossRefPubMedGoogle Scholar
  71. Kim WS, Ordija CM, Freeman MW (2003) Activation of signaling pathways by putative scavenger receptor class A (SR-A) ligands requires CD14 but not SR-A. Biochem Biophys Res Commun 310:542–549PubMedCrossRefGoogle Scholar
  72. Kim S, Watarai M, Suzuki H, Makino S, Kodama T, Shirahata T (2004) Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus. Microbial Pathog 37:11–19. CrossRefGoogle Scholar
  73. Kimbrell DA, Beutler B (2001) The evolution and genetics of innate immunity. Nat Rev Genet 2:256–267. [pii]CrossRefPubMedGoogle Scholar
  74. Kirii H et al (2003) Lack of interleukin-1beta decreases the severity of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 23:656–660 doi:10.1161/01.ATV.0000064374.15232.C301.ATV.0000064374.15232.C3[pii]PubMedCrossRefGoogle Scholar
  75. Kneidl J, Loffler B, Erat MC, Kalinka J, Peters G, Roth J, Barczyk K (2012) Soluble CD163 promotes recognition, phagocytosis and killing of Staphylococcus aureus via binding of specific fibronectin peptides. Cell Microbiol 14:914–936. CrossRefPubMedGoogle Scholar
  76. Kobayashi K, Hernandez LD, Galan JE, Janeway CA Jr, Medzhitov R, Flavell RA (2002a) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110:191–202PubMedCrossRefGoogle Scholar
  77. Kobayashi K et al (2002b) RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416:194–199 doi:10.1038/416194a416194a[pii]PubMedCrossRefGoogle Scholar
  78. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, Flavell RA (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307:731–734 doi:307/5710/731 [pii]10.1126/science.1104911PubMedCrossRefGoogle Scholar
  79. Koch M, Chitayat S, Dattilo BM, Schiefner A, Diez J, Chazin WJ, Fritz G (2010) Structural basis for ligand recognition and activation of RAGE. Structure 18:1342–1352. CrossRefPubMedPubMedCentralGoogle Scholar
  80. Krieg A et al (2009) XIAP mediates NOD signaling via interaction with RIP2. Proc Natl Acad Sci U S A 106:14524–14529 doi:0907131106 [pii]10.1073/pnas.0907131106PubMedPubMedCentralCrossRefGoogle Scholar
  81. Kzhyshkowska J, Neyen C, Gordon S (2012) Role of macrophage scavenger receptors in atherosclerosis. Immunobiology 217:492–502. CrossRefPubMedGoogle Scholar
  82. Lagathu C, Yvan-Charvet L, Bastard JP, Maachi M, Quignard-Boulange A, Capeau J, Caron M (2006) Long-term treatment with interleukin-1beta induces insulin resistance in murine and human adipocytes. Diabetologia 49:2162–2173. CrossRefPubMedGoogle Scholar
  83. Lamkanfi M et al (2009) Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J Cell Biol 187:61–70 doi:jcb.200903124 [pii]10.1083/jcb.200903124PubMedPubMedCentralCrossRefGoogle Scholar
  84. Laroui H et al (2011) L-Ala-gamma-D-Glu-meso-diaminopimelic acid (DAP) interacts directly with leucine-rich region domain of nucleotide-binding oligomerization domain 1, increasing phosphorylation activity of receptor-interacting serine/threonine-protein kinase 2 and its interaction with nucleotide-binding oligomerization domain 1. J Biol Chem 286:31003–31013 doi:M111.257501 [pii]10.1074/jbc.M111.257501PubMedPubMedCentralCrossRefGoogle Scholar
  85. Lee JG, Lim EJ, Park DW, Lee SH, Kim JR, Baek SH (2008) A combination of Lox-1 and Nox1 regulates TLR9-mediated foam cell formation. Cell Signal 20:2266–2275. CrossRefPubMedGoogle Scholar
  86. Lee GS et al (2013) The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP. Nature 492:123–127 doi:nature11588 [pii]10.1038/nature11588CrossRefGoogle Scholar
  87. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86:973–983PubMedCrossRefGoogle Scholar
  88. Lightfield KL et al (2008) Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin. Nat Immunol 9:1171–1178 doi:ni.1646 [pii]10.1038/ni.1646PubMedPubMedCentralCrossRefGoogle Scholar
  89. Lightfield KL et al (2011) Differential requirements for NAIP5 in activation of the NLRC4 inflammasome. Infect Immun 79:1606–1614 doi:IAI.01187-10 [pii]10.1128/IAI.01187-10PubMedPubMedCentralCrossRefGoogle Scholar
  90. Lubrano V, Balzan S (2014) LOX-1 and ROS, inseparable factors in the process of endothelial damage. Free radical Res 48:841–848. CrossRefGoogle Scholar
  91. Mandrup-Poulsen T, Pickersgill L, Donath MY (2010) Blockade of interleukin 1 in type 1 diabetes mellitus. Nat Rev Endocrinol 6:158–166 doi:nrendo.2009.271 [pii]10.1038/nrendo.2009.271PubMedCrossRefGoogle Scholar
  92. Mariathasan S et al (2004) Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430:213–218 doi:10.1038/nature02664nature02664[pii]PubMedCrossRefGoogle Scholar
  93. Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417–426 doi:S1097-2765(02)00599-3[pii]PubMedCrossRefGoogle Scholar
  94. Matloubian M, David A, Engel S, Ryan JE, Cyster JG (2000) A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol 1:298–304. CrossRefPubMedGoogle Scholar
  95. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145. CrossRefPubMedGoogle Scholar
  96. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394–397. CrossRefPubMedGoogle Scholar
  97. Mehta JL, Chen J, Hermonat PL, Romeo F, Novelli G (2006) Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders. Cardiovasc Res 69:36–45. CrossRefPubMedGoogle Scholar
  98. Miao EA et al (2010) Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc Natl Acad Sci U S A 107:3076–3080 doi:0913087107 [pii]10.1073/pnas.0913087107PubMedPubMedCentralCrossRefGoogle Scholar
  99. Moore KJ, Freeman MW (2006) Scavenger receptors in atherosclerosis: beyond lipid uptake. Arterioscler Thromb Vasc Biol 26:1702–1711. CrossRefPubMedGoogle Scholar
  100. Mukhopadhyay S, Peiser L, Gordon S (2004) Activation of murine macrophages by Neisseria meningitidis and IFN-gamma in vitro: distinct roles of class A scavenger and Toll-like pattern recognition receptors in selective modulation of surface phenotype. J Leukocyte Biol 76:577–584. CrossRefPubMedGoogle Scholar
  101. Mukhopadhyay S et al (2006) MARCO, an innate activation marker of macrophages, is a class A scavenger receptor for Neisseria meningitidis. Eur J Immunol 36:940–949. CrossRefPubMedGoogle Scholar
  102. Mukhopadhyay S, Varin A, Chen Y, Liu B, Tryggvason K, Gordon S (2011) SR-A/MARCO-mediated ligand delivery enhances intracellular TLR and NLR function, but ligand scavenging from cell surface limits TLR4 response to pathogens. Blood 117:1319–1328. CrossRefPubMedGoogle Scholar
  103. Murakami T, Ockinger J, Yu J, Byles V, McColl A, Hofer AM, Horng T (2012) Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci U S A 109:11282–11287 doi:1117765109 [pii]10.1073/pnas.1117765109PubMedPubMedCentralCrossRefGoogle Scholar
  104. Murshid A, Borges TJ, Calderwood SK (2015a) Emerging roles for scavenger receptor SREC-I in immunity. Cytokine 75:256–260. CrossRefPubMedPubMedCentralGoogle Scholar
  105. Murshid A, Gong J, Prince T, Borges TJ, Calderwood SK (2015b) Scavenger receptor SREC-I mediated entry of TLR4 into lipid microdomains and triggered inflammatory cytokine release in RAW 264.7 cells upon LPS activation. PloS one 10:e0122529. CrossRefPubMedPubMedCentralGoogle Scholar
  106. Murshid A, Borges TJ, Lang BJ, Calderwood SK (2016) The scavenger receptor SREC-I cooperates with toll-like receptors to trigger inflammatory innate immune responses. Front Immunol 7:226. CrossRefPubMedPubMedCentralGoogle Scholar
  107. Nakamura T, Suzuki H, Wada Y, Kodama T, Doi T (2006) Fucoidan induces nitric oxide production via p38 mitogen-activated protein kinase and NF-kappaB-dependent signaling pathways through macrophage scavenger receptors. Biochem Biophysl Res Commun 343:286–294. CrossRefGoogle Scholar
  108. Ohki I et al (2005) Crystal structure of human lectin-like, oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL. Structure 13:905–917. CrossRefPubMedGoogle Scholar
  109. O’Neill LA, Bryant CE, Doyle SL (2009) Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev 61:177–197 doi:pr.109.001073 [pii]10.1124/pr.109.001073PubMedPubMedCentralCrossRefGoogle Scholar
  110. O’Neill LA, Golenbock D, Bowie AG (2013) The history of Toll-like receptors - redefining innate immunity. Nat Rev Immunol 13:453–460 doi:nri3446 [pii]10.1038/nri3446PubMedCrossRefGoogle Scholar
  111. Opitz B et al (2004) Nucleotide-binding oligomerization domain proteins are innate immune receptors for internalized Streptococcus pneumoniae. J Biol Chem 279:36426–36432 doi:10.1074/jbc.M403861200M403861200[pii]PubMedCrossRefGoogle Scholar
  112. Opitz B et al (2005) Nod1-mediated endothelial cell activation by Chlamydophila pneumoniae. Circ Res 96:319–326 doi:01.RES.0000155721.83594.2c [pii]10.1161/01.RES.0000155721.83594.2cPubMedCrossRefGoogle Scholar
  113. Palma AS et al (2006) Ligands for the beta-glucan receptor, Dectin-1, assigned using “designer” microarrays of oligosaccharide probes (neoglycolipids) generated from glucan polysaccharides. J Biol Chem 281:5771–5779. CrossRefPubMedGoogle Scholar
  114. Park H, Adsit FG, Boyington JC (2005) The 1.4 angstrom crystal structure of the human oxidized low density lipoprotein receptor lox-1. J Biol Chem 280:13593–13599. CrossRefPubMedGoogle Scholar
  115. Park JH et al (2007) RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. J Immunol 178:2380–2386 doi:178/4/2380[pii]PubMedCrossRefGoogle Scholar
  116. Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25:5071–5082 doi:7601378 [pii]10.1038/sj.emboj.7601378PubMedPubMedCentralCrossRefGoogle Scholar
  117. Pepino MY, Kuda O, Samovski D, Abumrad NA (2014) Structure-function of CD36 and importance of fatty acid signal transduction in fat metabolism. Ann Rev Nutr 34:281–303. CrossRefGoogle Scholar
  118. Pickup JC (2004) Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27:813–823PubMedCrossRefGoogle Scholar
  119. Pikkarainen T, Brannstrom A, Tryggvason K (1999) Expression of macrophage MARCO receptor induces formation of dendritic plasma membrane processes. J Biol Chem 274:10975–10982PubMedCrossRefGoogle Scholar
  120. Pluddemann A et al (2009) SR-A, MARCO and TLRs differentially recognise selected surface proteins from Neisseria meningitidis: an example of fine specificity in microbial ligand recognition by innate immune receptors. J Innate Immun 1:153–163. CrossRefPubMedGoogle Scholar
  121. Poltorak A et al (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088PubMedPubMedCentralCrossRefGoogle Scholar
  122. Popescu BF, Lucchinetti CF (2012) Pathology of demyelinating diseases. Ann Rev Pathol 7:185–217. CrossRefGoogle Scholar
  123. Prabhudas M et al (2014) Standardizing scavenger receptor nomenclature. J Immunol 192:1997–2006. CrossRefPubMedPubMedCentralGoogle Scholar
  124. Qu Y et al (2011) Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J Immunol 186:6553–6561 doi:jimmunol.1100478 [pii]10.4049/jimmunol.1100478PubMedCrossRefGoogle Scholar
  125. Qureshi S, Medzhitov R (2003) Toll-like receptors and their role in experimental models of microbial infection. Genes Immun 4:87–94 doi:10.1038/sj.gene.63639376363937[pii]PubMedCrossRefGoogle Scholar
  126. Resnick D, Chatterton JE, Schwartz K, Slayter H, Krieger M (1996) Structures of class A macrophage scavenger receptors. Electron microscopic study of flexible, multidomain, fibrous proteins and determination of the disulfide bond pattern of the scavenger receptor cysteine-rich domain. J Biol Chem 271:26924–26930PubMedCrossRefGoogle Scholar
  127. Sakaguchi M et al (2011) TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding. PloS One 6:e23132. CrossRefPubMedPubMedCentralGoogle Scholar
  128. Schaefer L et al (2005) The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J Clin Invest 115:2223–2233. CrossRefPubMedPubMedCentralGoogle Scholar
  129. Schorey JS, Lawrence C (2008) The pattern recognition receptor Dectin-1: from fungi to mycobacteria. Curr Drug Targets 9:123–129PubMedPubMedCentralCrossRefGoogle Scholar
  130. Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832 doi:S0092-8674(10)00075-9 [pii]10.1016/j.cell.2010.01.040PubMedCrossRefGoogle Scholar
  131. Shimaoka T, Kume N, Minami M, Hayashida K, Sawamura T, Kita T, Yonehara S (2001) LOX-1 supports adhesion of Gram-positive and Gram-negative bacteria. J Immunol 166:5108–5114PubMedCrossRefGoogle Scholar
  132. Shimaoka T et al (2003) Cutting edge: SR-PSOX/CXC chemokine ligand 16 mediates bacterial phagocytosis by APCs through its chemokine domain. J Immunol 171:1647–1651PubMedCrossRefGoogle Scholar
  133. Silverstein RL, Febbraio M (2009) CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal 2:re3. CrossRefPubMedPubMedCentralGoogle Scholar
  134. Slack JL, Schooley K, Bonnert TP, Mitcham JL, Qwarnstrom EE, Sims JE, Dower SK (2000) Identification of two major sites in the type I interleukin-1 receptor cytoplasmic region responsible for coupling to pro-inflammatory signaling pathways. J Biol Chem 275:4670–4678PubMedCrossRefGoogle Scholar
  135. Slauenwhite D, Johnston B (2015) Regulation of NKT cell localization in homeostasis and infection. Front Immunol 6:255. CrossRefPubMedPubMedCentralGoogle Scholar
  136. Stewart CR et al (2010) CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol 11:155–161. CrossRefPubMedGoogle Scholar
  137. Supajatura V, Ushio H, Nakao A, Akira S, Okumura K, Ra C, Ogawa H (2002) Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity. J Clin Invest 109:1351–1359. CrossRefPubMedPubMedCentralGoogle Scholar
  138. Takeda K, Akira S (2005) Toll-like receptors in innate immunity. Int Immunol 17:1–14 doi:17/1/1 [pii]10.1093/intimm/dxh186PubMedPubMedCentralCrossRefGoogle Scholar
  139. Tamura Y et al (2004) Scavenger receptor expressed by endothelial cells I (SREC-I) mediates the uptake of acetylated low density lipoproteins by macrophages stimulated with lipopolysaccharide. J Biol Chem 279:30938–30944. CrossRefPubMedGoogle Scholar
  140. Thakkar S, Wang X, Khaidakov M, Dai Y, Gokulan K, Mehta JL, Varughese KI (2015) Structure-based design targeted at LOX-1, a receptor for oxidized low-density lipoprotein. Sci Rep 5:16740. CrossRefPubMedPubMedCentralGoogle Scholar
  141. Triantafilou M, Gamper FG, Haston RM, Mouratis MA, Morath S, Hartung T, Triantafilou K (2006) Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J Biol Chem 281:31002–31011. CrossRefPubMedGoogle Scholar
  142. Viala J et al (2004) Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 5:1166–1174 doi:ni1131 [pii]10.1038/ni1131PubMedCrossRefGoogle Scholar
  143. West AP et al (2011) TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 472:476–480 doi:nature09973 [pii]10.1038/nature09973PubMedPubMedCentralCrossRefGoogle Scholar
  144. Wilkinson K, El Khoury J (2012) Microglial scavenger receptors and their roles in the pathogenesis of Alzheimer’s disease. Int J Alzheimer’s Dis 2012:489456. CrossRefGoogle Scholar
  145. Wittel UA et al (2015) The chemokine ligand CXCL16 is an indicator of bacterial infection in necrotizing pancreatitis. Pancreatol: Off J Int Assoc Pancreatol 15:124–130. CrossRefGoogle Scholar
  146. Wu Z, Sawamura T, Kurdowska AK, Ji HL, Idell S, Fu J (2011) LOX-1 deletion improves neutrophil responses, enhances bacterial clearance, and reduces lung injury in a murine polymicrobial sepsis model. Infect Immun 79:2865–2870. CrossRefPubMedPubMedCentralGoogle Scholar
  147. Xu Y, Tao X, Shen B, Horng T, Medzhitov R, Manley JL, Tong L (2000) Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408:111–115. CrossRefPubMedGoogle Scholar
  148. Xu H, Xu W, Chu Y, Gong Y, Jiang Z, Xiong S (2005) Involvement of up-regulated CXC chemokine ligand 16/scavenger receptor that binds phosphatidylserine and oxidized lipoprotein in endotoxin-induced lethal liver injury via regulation of T-cell recruitment and adhesion. Infect Immun 73:4007–4016. CrossRefPubMedPubMedCentralGoogle Scholar
  149. Yamamoto Y et al (2011) Septic shock is associated with receptor for advanced glycation end products ligation of LPS. J Immunol 186:3248–3257. CrossRefPubMedGoogle Scholar
  150. Yu M et al (2006) HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock 26:174–179 doi:10.1097/01.shk.0000225404.51320.8200024382-200608000-00011[pii]PubMedCrossRefGoogle Scholar
  151. Zaki MH, Boyd KL, Vogel P, Kastan MB, Lamkanfi M, Kanneganti TD (2010) The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 32:379–391 doi:S1074-7613(10)00086-5 [pii]10.1016/j.immuni.2010.03.003PubMedPubMedCentralCrossRefGoogle Scholar
  152. Zani IA, Stephen SL, Mughal NA, Russell D, Homer-Vanniasinkam S, Wheatcroft SB, Ponnambalam S (2015) Scavenger receptor structure and function in health and disease. Cells 4:178–201. CrossRefPubMedPubMedCentralGoogle Scholar
  153. Zarember KA, Godowski PJ (2002) Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J Immunol 168:554–561PubMedCrossRefGoogle Scholar
  154. Zhao W, Ma G, Chen X (2014) Lipopolysaccharide induced LOX-1 expression via TLR4/MyD88/ROS activated p38MAPK-NF-kappaB pathway. Vasc Pharmacol 63:162–172. CrossRefGoogle Scholar
  155. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J (2010) Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol 11:136–140 doi:ni.1831 [pii]10.1038/ni.1831CrossRefGoogle Scholar
  156. Zhu XD et al (2011) Caveolae-dependent endocytosis is required for class A macrophage scavenger receptor-mediated apoptosis in macrophages. J Biol chem 286:8231–8239. CrossRefPubMedPubMedCentralGoogle Scholar
  157. Zilbauer M et al (2007) A major role for intestinal epithelial nucleotide oligomerization domain 1 (NOD1) in eliciting host bactericidal immune responses to Campylobacter jejuni. Cell Microbiol 9:2404–2416 doi:CMI969 [pii]10.1111/j.1462-5822.2007.00969.xPubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Aakanksha Gulati
    • 1
  • Deepinder Kaur
    • 1
  • G. V. R. Krishna Prasad
    • 1
  • Arunika Mukhopadhaya
    • 1
    Email author
  1. 1.Department of Biological SciencesIndian Institute of Science Education and Research (IISER) MohaliMohaliIndia

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