Pattern-Recognition Receptor Signaling Initiated From Extracellular, Membrane, and Cytoplasmic Space

  • Lee, Myeong Sup (Department of Biochemistry, Yonsei University) ;
  • Kim, Young-Joon (Department of Biochemistry, Yonsei University)
  • Received : 2007.01.29
  • Accepted : 2007.01.31
  • Published : 2007.02.28

Abstract

Invading pathogens are recognized by diverse germline-encoded pattern-recognition receptors (PRRs) which are distributed in three different cellular compartments: extracellular, membrane, and cytoplasmic. In mammals, the major extracellular PRRs such as complements may first encounter the invading pathogens and opsonize them for clearance by phagocytosis which is mediated by membrane-associated phagocytic receptors including complement receptors. The major membrane-associated PRRs, Toll-like receptors, recognize diverse pathogens and generate inflammatory signals to coordinate innate immune responses and shape adaptive immune responses. Furthemore, certain membrane-associated PRRs such as Dectin-1 can mediate phagocytosis and also induce inflammatory response. When these more forefront detection systems are avoided by the pathogens, cytoplasmic PRRs may play major roles. Cytoplasmic caspase-recruiting domain (CARD) helicases such as retinoic acid-inducible protein I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5), mediate antiviral immunity by inducing the production of type I interferons. Certain members of nucleotide-binding oligomerization domain (NOD)-like receptors such as NALP3 present in the cytosol form inflammasomes to induce inflammatory responses upon ligand recognition. Thus, diverse families of PRRs coordinately mediate immune responses against diverse types of pathogens.

Keywords

CARD Helicase;Complement Receptor;Dectin-1;Innate Immunity;NOD-like Receptor;Pattern-Recognition Receptor;Toll-like Receptor

Acknowledgement

Supported by : Korean Ministry of Science and Technology, Korean Ministry of Education

References

  1. Aderem, A. and Underhill, D. M. (1999) Mechanisms of phagocytosis in macrophages. Annu. Rev. Immunol. 17, 593−623
  2. Akira, S. and Takeda, K. (2004) Toll-like receptor signalling. Nat. Rev. Immunol. 4, 499-511 https://doi.org/10.1038/nri1391
  3. Akira, S., Uematsu, S., and Takeuchi, O. (2006) Pathogen recognition and innate immunity. Cell 124, 783−801 https://doi.org/10.1016/j.cell.2005.12.028
  4. Caron, E. and Hall, A. (1998) Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 282, 1717−1721 https://doi.org/10.1126/science.282.5397.1
  5. Chen, Z. J. (2005) Ubiquitin signalling in the NF-kappaB pathway. Nat. Cell Biol. 7, 758−765
  6. ranchi, L., Amer, A., Body-Malapel, M., Kanneganti, T. D., Ozoren, N., et al. (2006) Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonellainfected macrophages. Nat. Immunol. 7, 576-582 https://doi.org/10.1038/ni1346
  7. Gagnon, E., Duclos, S., Rondeau, C., Chevet, E., Cameron, P. H., et al. (2002) Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages. Cell 110, 119− 131 https://doi.org/10.1016/S0092-8674(02)00821-8
  8. awlisch, H. and Kohl, J. (2006) Complement and Toll-like receptors: key regulators of adaptive immune responses. Mol. Immunol. 43, 13-21 https://doi.org/10.1016/j.molimm.2005.06.028
  9. Kagan, J. C. and Medzhitov, R. (2006) Phosphoinositidemediated adaptor recruitment controls Toll-like receptor signaling. Cell 125, 943−955
  10. Kato, H., Sato, S., Yoneyama, M., Yamamoto, M., Uematsu, S., et al. (2005) Cell type-specific involvement of RIG-I in antiviral response. Immunity 23, 19−28
  11. Kobayashi, K. S., Chamaillard, M., Ogura, Y., Henegariu, O., Inohara, N., et al. (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731−734
  12. Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., et al. (2006) Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440, 228−232
  13. Martinon, F. and Tschopp, J. (2005) NLRs join TLRs as innate sensors of pathogens. Trends Immunol. 26, 447−454
  14. May, R. C. and Machesky, L. M. (2001) Phagocytosis and the actin cytoskeleton. J. Cell Sci. 114, 1061−1077
  15. eylan, E., Burns, K., Hofmann, K., Blancheteau, V., Martinon, F., et al. (2004) RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat. Immunol. 5, 503-507 https://doi.org/10.1038/ni1061
  16. Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., et al. (2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437, 1167−1172
  17. Murray, R. Z., Kay, J. G., Sangermani, D. G., and Stow, J. L. (2005) A role for the phagosome in cytokine secretion. Science 310, 1492−1495 https://doi.org/10.1126/science.1118435
  18. Niedergang, F. and Chavrier, P. (2004) Signaling and membrane dynamics during phagocytosis: many roads lead to the phagos(R)ome. Curr. Opin. Cell Biol. 16, 422−428
  19. Perianayagam, M. C., Balakrishnan, V. S., Pereira, B. J., and Jaber, B. L. (2004) C5a delays apoptosis of human neutrophils via an extracellular signal-regulated kinase and Badmediated signalling pathway. Eur. J. Clin. Invest. 34, 50−56
  20. aijo, S., Fujikado, N., Furuta, T., Chung, S. H., Kotaki, H., et al. (2007) Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat. Immunol. 8, 39-46 https://doi.org/10.1038/ni1425
  21. Stark, G. R., Kerr, I. M., Williams, B. R., Silverman, R. H., and Schreiber, R. D. (1998) How cells respond to interferons. Annu. Rev. Biochem. 67, 227−264
  22. Takaoka, A., Yanai, H., Kondo, S., Duncan, G., Negishi, H., et al. (2005) Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 434, 243− 249
  23. Taylor, P. R., Martinez-Pomares, L., Stacey, M., Lin, H. H., Brown, G. D., et al. (2005) Macrophage receptors and immune recognition. Annu. Rev. Immunol. 23, 901−944
  24. Crowley, M. T., Costello, P. S., Fitzer-Attas, C. J., Turner, M., Meng, F., et al. (1997) A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages. J. Exp. Med. 186, 1027−1039
  25. Hall, A. B., Gakidis, M. A., Glogauer, M., Wilsbacher, J. L., Gao, S., et al. (2006) Requirements for Vav guanine nucleotide exchange factors and Rho GTPases in FcgammaR- and complement-mediated phagocytosis. Immunity 24, 305−316
  26. Bohana-Kashtan, O., Ziporen, L., Donin, N., Kraus, S., and Fishelson, Z. (2004) Cell signals transduced by complement. Mol. Immunol. 41, 583−597 https://doi.org/10.1016/j.molimm.2004.03.001
  27. Cox, D., Tseng, C. C., Bjekic, G., and Greenberg, S. (1999) A requirement for phosphatidylinositol 3-kinase in pseudopod extension. J. Biol. Chem. 274, 1240−1247
  28. Gantner, B. N., Simmons, R. M., Canavera, S. J., Akira, S., and Underhill, D. M. (2003) Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J. Exp. Med. 197, 1107−1117 https://doi.org/10.1084/jem.20021964
  29. Oganesyan, G., Saha, S. K., Guo, B., He, J. Q., Shahangian, A., et al. (2006) Critical role of TRAF3 in the Toll-like receptordependent and -independent antiviral response. Nature 439, 208−211
  30. Ross, F. P. and Teitelbaum, S. L. (2005) alphavbeta3 and macrophage colony-stimulating factor: partners in osteoclast biology. Immunol. Rev. 208, 88−105
  31. Touret, N., Paroutis, P., Terebiznik, M., Harrison, R. E., Trombetta, S., et al. (2005) Quantitative and dynamic assessment of the contribution of the ER to phagosome formation. Cell 123, 157−170
  32. Andrejeva, J., Childs, K. S., Young, D. F., Carlos, T. S., Stock, N., et al. (2004) The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc. Natl. Acad. Sci. USA 101, 17264−17269
  33. Inohara, Chamaillard, McDonald, C., and Nunez, G. (2005) NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. Annu. Rev. Biochem. 74, 355−383
  34. ogers, N. C., Slack, E. C., Edwards, A. D., Nolte, M. A., Schulz, O., et al. (2005) Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 22, 507-517 https://doi.org/10.1016/j.immuni.2005.03.004
  35. Underhill, D. M., Rossnagle, E., Lowell, C. A., and Simmons, R. M. (2005) Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood 106, 2543−2550 https://doi.org/10.1182/blood-2005-04-1434
  36. Gasque, P. (2004) Complement: a unique innate immune sensor for danger signals. Mol. Immunol. 41, 1089−1098 https://doi.org/10.1016/j.molimm.2004.03.001
  37. May, R. C., Caron, E., Hall, A., and Machesky, L. M. (2000) Involvement of the Arp2/3 complex in phagocytosis mediated by FcgammaR or CR3. Nat. Cell. Biol. 2, 246−248
  38. trober, W., Murray, P. J., Kitani, A., and Watanabe, T. (2006) Signalling pathways and molecular interactions of NOD1 and NOD2. Nat. Rev. Immunol. 6, 9-20 https://doi.org/10.1038/nri1747
  39. Xu, L. G., Wang, Y. Y., Han, K. J., Li, L. Y., Zhai, Z., et al. (2005) VISA is an adapter protein required for virustriggered IFN-beta signaling. Mol. Cells 19, 727−740
  40. Bokoch, G. M. and Diebold, B. A. (2002) Current molecular models for NADPH oxidase regulation by Rac GTPase. Blood 100, 2692−2696 https://doi.org/10.1182/blood-2002-09-2722
  41. Brown, G. D. (2006) Dectin-1: a signalling non-TLR patternrecognition receptor. Nat. Rev. Immunol. 6, 33−43
  42. Kawai, T. and Akira, S. (2006b) TLR signaling. Cell Death Differ. 13, 816−825
  43. Molofsky, A. B., Byrne, B. G., Whitfield, N. N., Madigan, C. A., Fuse, E. T., et al. (2006) Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection. J. Exp. Med. 203, 1093−1104
  44. Janeway, C. A., Jr. and Medzhitov, R. (2002) Innate immune recognition. Annu. Rev. Immunol. 20, 197−216
  45. Pichlmair, A., Schulz, O., Tan, C. P., Naslund, T. I., Liljestrom, P., et al. (2006) RIG-I-mediated antiviral responses to singlestranded RNA bearing 5′-phosphates. Science 314, 997−1001
  46. Gitlin, L., Barchet, W., Gilfillan, S., Cella, M., Beutler, B., et al. (2006) Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc. Natl. Acad. Sci. USA 103, 8459−8464
  47. Hacker, H., Redecke, V., Blagoev, B., Kratchmarova, I., Hsu, L. C., et al. (2006) Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature 439, 204−207
  48. Iwasaki, A. and Medzhitov, R. (2004) Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5, 987-995 https://doi.org/10.1038/ni1112
  49. Wu, Y., Tibrewal, N., and Birge, R. B. (2006) Phosphatidylserine recognition by phagocytes: a view to a kill. Trends Cell Biol. 16, 189−197
  50. Buhl, A. M., Avdi, N., Worthen, G. S., and Johnson, G. L. (1994) Mapping of the C5a receptor signal transduction network in human neutrophils. Proc. Natl. Acad. Sci. USA 91, 9190− 9194
  51. Carroll, M. C. (2004) The complement system in regulation of adaptive immunity. Nat. Immunol. 5, 981−986
  52. Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., et al. (2000) Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103, 351−361 https://doi.org/10.1016/S0092-8674(00)00097-0
  53. ato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., et al. (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441, 101-105 https://doi.org/10.1038/nature04734
  54. Kawai, T. and Akira, S. (2006a) Innate immune recognition of viral infection. Nat. Immunol. 7, 131−137
  55. Werts, C., Girardin, S. E., and Philpott, D. J. (2006) TIR, CARD and PYRIN: three domains for an antimicrobial triad. Cell Death Differ. 13, 798−815
  56. Martinon, F. and Tschopp, J. (2004) Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell 117, 561−574
  57. Sun, Q., Sun, L., Liu, H. H., Chen, X., Seth, R. B., et al. (2006) The specific and essential role of MAVS in antiviral innate immune responses. Immunity 24, 633−642
  58. Castellano, F., Le Clainche, C., Patin, D., Carlier, M. F., and Chavrier, P. (2001) A WASp-VASP complex regulates actin polymerization at the plasma membrane. EMBO J. 20, 5603− 5614 https://doi.org/10.1093/emboj/20.1.1
  59. awai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., et al. (2005) IPS-1, an adaptor triggering RIG-I- and Mda5- mediated type I interferon induction. Nat. Immunol. 6, 981- 988 https://doi.org/10.1038/ni1243
  60. Cusson-Hermance, N., Khurana, S., Lee, T. H., Fitzgerald, K. A., and Kelliher, M. A. (2005) Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation. J. Biol. Chem. 280, 36560−36566 https://doi.org/10.1074/jbc.R400035200
  61. Lofgren, R., Serrander, L., Forsberg, M., Wilsson, A., Wasteson, A., et al. (1999) CR3, FcgammaRIIA and FcgammaRIIIB induce activation of the respiratory burst in human neutrophils: the role of intracellular Ca(2+), phospholipase D and tyrosine phosphorylation. Biochim. Biophys. Acta 1452, 46−59
  62. ang, C., Deng, L., Hong, M., Akkaraju, G. R., Inoue, J., et al. (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-351 https://doi.org/10.1038/35085597
  63. Seth, R. B., Sun, L., Ea, C. K., and Chen, Z. J. (2005) Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 122, 669−682
  64. Medzhitov, R. and Janeway, C. A., Jr. (2002) Decoding the patterns of self and nonself by the innate immune system. Science 296, 298−300
  65. Perianayagam, M. C., Balakrishnan, V. S., King, A. J., Pereira, B. J., and Jaber, B. L. (2002). C5a delays apoptosis of human neutrophils by a phosphatidylinositol 3-kinase-signaling pathway. Kidney Int. 61, 456−463 https://doi.org/10.1046/j.1523-1755.2002.00085.x
  66. Ren, T., Zamboni, D. S., Roy, C. R., Dietrich, W. F., and Vance, R. E. (2006) Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity. PLoS Pathog. 2, e18 https://doi.org/10.1371/journal.ppat.0020001
  67. Ishii, K. J., Coban, C., Kato, H., Takahashi, K., Torii, Y., et al. (2006) A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Nat. Immunol. 7, 40−48
  68. Martinon, F., Petrilli, V., Mayor, A., Tardivel, A., and Tschopp, J. (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237−241
  69. Rowe, D. C., McGettrick, A. F., Latz, E., Monks, B. G., Gay, N. J., et al. (2006) The myristoylation of TRIF-related adaptor molecule is essential for Toll-like receptor 4 signal transduction. Proc. Natl. Acad. Sci. USA 103, 6299−6304
  70. ato, S., Sanjo, H., Takeda, K., Ninomiya-Tsuji, J., Yamamoto, M., et al. (2005) Essential function for the kinase TAK1 in innate and adaptive immune responses. Nat. Immunol. 6, 1087-1095 https://doi.org/10.1038/ni1255
  71. Ting, J. P., Kastner, D. L., and Hoffman, H. M. (2006) CATERPILLERs, pyrin and hereditary immunological disorders. Nat. Rev. Immunol. 6, 183−195 https://doi.org/10.1038/nrm1608
  72. Kanneganti, T. D., Ozoren, N., Body-Malapel, M., Amer, A., Park, J. H., et al. (2006) Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440, 233−236
  73. Pulendran, B. and Ahmed, R. (2006) Translating innate immunity into immunological memory: implications for vaccine development. Cell 124, 849−863
  74. Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., et al. (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 5, 730−737
  75. Garlanda, C., Bottazzi, B., Bastone, A., and Mantovani, A. (2005) Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu. Rev. Immunol. 23, 337−366
  76. irardin, S. E., Tournebize, R., Mavris, M., Page, A. L., Li, X., et al. (2001) CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri. EMBO Rep. 2, 736- 742 https://doi.org/10.1093/embo-reports/kve155
  77. Perianayagam, M. C., Madias, N. E., Pereira, B. J., and Jaber, B. L. (2006) CREB transcription factor modulates Bcl2 transcription in response to C5a in HL-60-derived neutrophils. Eur. J. Clin. Invest. 36, 353−361
  78. aylor, P. R., Tsoni, S. V., Willment, J. A., Dennehy, K. M., Rosas, M., et al. (2007) Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat. Immunol. 8, 31-38 https://doi.org/10.1038/ni1408
  79. Gross, O., Gewies, A., Finger, K., Schafer, M., Sparwasser, T., et al. (2006) Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 442, 651−656
  80. Hornung, V., Ellegast, J., Kim, S., Brzozka, K., Jung, A., et al. (2006) 5′-Triphosphate RNA is the ligand for RIG-I. Science 314, 994−997
  81. Swanson, J. A. and Hoppe, A. D. (2004) The coordination of signaling during Fc receptor-mediated phagocytosis. J. Leukoc. Biol. 76, 1093−1103
  82. Underhill, D. M. and Ozinsky, A. (2002) Phagocytosis of microbes: complexity in action. Annu. Rev. Immunol. 20, 825−852
  83. Tschopp, J., Martinon, F., and Burns, K. (2003) NALPs: a novel protein family involved in inflammation. Nat. Rev. Mol. Cell Biol. 4, 95−104
  84. Greenberg, S. (1999) Modular components of phagocytosis. J. Leukoc. Biol. 66, 712−717
  85. Guo, R. F. and Ward, P. A. (2005) Role of C5a in inflammatory responses. Annu. Rev. Immunol. 23, 821−852
  86. iao, E. A., Alpuche-Aranda, C. M., Dors, M., Clark, A. E., Bader, M. W., et al. (2006) Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf. Nat. Immunol. 7, 569-575 https://doi.org/10.1038/ni1344
  87. Saha, S. K., Pietras, E. M., He, J. Q., Kang, J. R., Liu, S. Y., et al. (2006) Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif. EMBO J. 25, 3257−3263