DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway

English version České info

Pathogen-associated molecular patterns (PAMPs) trigger host immune response by activating pattern recognition receptors like toll-like receptors (TLRs). However, the mechanism whereby several pathogens, including viruses, activate TLRs via a non-PAMP mechanism is unclear. Endogenous “inflammatory mediators” called damage-associated molecular patterns (DAMPs) have been implicated in regulating immune response and inflammation. However, the role of DAMPs in inflammation/immunity during virus infection has not been studied. We have identified a DAMP molecule, S100A9 (also known as Calgranulin B or MRP-14), as an endogenous non-PAMP activator of TLR signaling during influenza A virus (IAV) infection. S100A9 was released from undamaged IAV-infected cells and extracellular S100A9 acted as a critical host-derived molecular pattern to regulate inflammatory response outcome and disease during infection by exaggerating pro-inflammatory response, cell-death and virus pathogenesis. Genetic studies showed that the DDX21-TRIF signaling pathway is required for S100A9 gene expression/production during infection. Furthermore, the inflammatory activity of extracellular S100A9 was mediated by activation of the TLR4-MyD88 pathway. Our studies have thus, underscored the role of a DAMP molecule (i.e. extracellular S100A9) in regulating virus-associated inflammation and uncovered a previously unknown function of the DDX21-TRIF-S100A9-TLR4-MyD88 signaling network in regulating inflammation during infection.

Vyšlo v časopise: DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway. PLoS Pathog 10(1): e32767. doi:10.1371/journal.ppat.1003848
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003848

Souhrn

Zdroje

1. KawaiT, AkiraS (2010) The role of pattern-recognition receptors in innate immunity: Update on toll-like receptors. Nat Immunol 11: 373–384.

2. McGettrickAF, O'NeillLAJ (2010) Localisation and trafficking of toll-like receptors: An important mode of regulation. Curr Opin Immunol 22: 20–27.

3. PiccininiAM, MidwoodKS (2010) DAMPening inflammation by modulating TLR signalling. Mediators Inflamm 2010: pii: 672395.

4. KunisakiKM, JanoffEN (2009) Influenza in immunosuppressed populations: A review of infection frequency, morbidity, mortality, and vaccine responses. Lancet Infect Dis 9: 493–504.

5. TscherneDM, Garcia-SastreA (2011) Virulence determinants of pandemic influenza viruses. J Clin Invest 121: 6–13.

6. RuuskanenO, LahtiE, JenningsLC, MurdochDR (2011) Viral pneumonia. Lancet 377: 1264–1275.

7. DawoodFS, IulianoAD, ReedC, MeltzerMI, ShayDK, et al. (2012) Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: A modelling study. Lancet Infect Dis 12: 687–695.

8. BoseS, BanerjeeAK (2003) Innate immune response negative strand against nonsegmented RNA viruses. J Interferon Cytokine Res 23: 401–412.

9. StarkGR, KerrIM, WilliamsBRG, SilvermanRH, SchreiberRD (1998) HOW CELLS RESPOND TO INTERFERONS. Annu Rev Biochem 67: 227–264.

10. UematsuS, AkiraS (2007) Toll-like receptors and type I interferons. J Biol Chem 282: 15319–15323.

11. VersteegGA, García-SastreA (2010) Viral tricks to grid-lock the type I interferon system. Curr Opin Microbiol 13: 508–516.

12. SchmolkeM, García-SastreA (2010) Evasion of innate and adaptive immune responses by influenza A virus. Cell Microbiol 12: 873–880.

13. WilkinsC, GaleMJr (2010) Recognition of viruses by cytoplasmic sensors. Curr Opin Immunol 22: 41–47.

14. BoseS, KarN, MaitraR, DiDonatoJA, BanerjeeAK (2003) Temporal activation of NF-κB regulates an interferon-independent innate antiviral response against cytoplasmic RNA viruses. Proc Natl Acad Sci USA 100: 10890–10895.

15. KotaS, SabbahA, ChangTH, HarnackR, XiangY, et al. (2008) Role of human beta-defensin-2 during tumor necrosis factor-alpha/NF-kappaB-mediated innate antiviral response against human respiratory syncytial virus. J Biol Chem 283: 22417–22429.

16. SegoviaJ, SabbahA, MgbemenaV, TsaiS, ChangT, et al. (2012) TLR2/MyD88/NF-κB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection. PLoS One 7: e29695.

17. IchinoheT (2010) Respective roles of TLR, RIG-I and NLRP3 in influenza virus infection and immunity: Impact on vaccine design. Expert Rev Vaccines 9: 1315–1324.

18. AllenIC, ScullMA, MooreCB, HollEK, McElvania-TeKippeE, et al. (2009) The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30: 556–565.

19. IchinoheT, LeeHK, OguraY, FlavellR, IwasakiA (2009) Inflammasome recognition of influenza virus is essential for adaptive immune responses. J Exp Med 206: 79–87.

20. KannegantiT, Body-MalapelM, AmerA, ParkJ, WhitfieldJ, et al. (2006) Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J Biol Chem 281: 36560–36568.

21. SabbahA, ChangTH, HarnackR, FrohlichV, TominagaK, et al. (2009) Activation of innate immune antiviral responses by Nod2. Nat Immunol 10: 1073–1080.

22. NhuQM, ShireyK, TeijaroJR, FarberDL, Netzel-ArnettS, et al. (2010) Novel signaling interactions between proteinase-activated receptor 2 and toll-like receptors in vitro and in vivo. Mucosal Immunol 3: 29–39.

23. ImaiY, KubaK, NeelyGG, Yaghubian-MalhamiR, PerkmannT, et al. (2008) Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 133: 235–249.

24. SeoS, KwonH, SongJ, ByunY, SeongBL, et al. (2010) MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection. J Virol 84: 12713–12722.

25. LooY, FornekJ, CrochetN, BajwaG, PerwitasariO, et al. (2008) Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol 82: 335–345.

26. Le GofficR, PothlichetJ, VitourD, FujitaT, MeursE, et al. (2007) Cutting edge: Influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells. J Immunol 178: 3368–3372.

27. LundJM, AlexopoulouL, SatoA, KarowM, AdamsNC, et al. (2004) Recognition of single-stranded RNA viruses by toll-like receptor 7. Proc Natl Acad Sci USA 101: 5598–5603.

28. GuillotL, Le GofficR, BlochS, EscriouN, AkiraS, et al. (2005) Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem 280: 5571–5580.

29. WangJP, BowenGN, PaddenC, CernyA, FinbergRW, et al. (2008) Toll-like receptor-mediated activation of neutrophils by influenza A virus. Blood 112: 2028–2034.

30. DieboldSS, KaishoT, HemmiH, AkiraS, Reis e SousaC (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303: 1529–1531.

31. KoyamaS, IshiiKJ, KumarH, TanimotoT, CobanC, et al. (2007) Differential role of TLR- and RLR-signaling in the immune responses to influenza A virus infection and vaccination. J Immunol 179: 4711–4720.

32. HinojosaCA, MgbemenaV, Van RoekelS, AustadSN, MillerRA, et al. (2012) Enteric-delivered rapamycin enhances resistance of aged mice to pneumococcal pneumonia through reduced cellular senescence. Exp Gerontol 47: 958–965.

33. KotaS, BasuM, BanerjeeAK, BoseS (2010) Role of human beta defensin 3 during type-I interferon mediated antiviral response. J Interferon Cytokine Med Res 2: 23–32.

34. BasuM, MaitraRK, XiangY, MengX, BanerjeeAK, et al. (2006) Inhibition of vesicular stomatitis virus infection in epithelial cells by interferon-alpha induced soluble secreted proteins. J Gen Virol 87: 2653–2662.

35. LiangSC, TanXY, LuxenbergDP, KarimR, Dunussi-JoannopoulosK, et al. (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203: 2271–2279.

36. BandoM, HiroshimaY, KataokaM, ShinoharaY, HerzbergMC, et al. (2007) Interleukin-1alpha regulates antimicrobial peptide expression in human keratinocytes. Immunol Cell Biol 85: 532–537.

37. McMorranBJ, PatatSA, CarlinJB, GrimwoodK, JonesA, et al. (2007) Novel neutrophil-derived proteins in bronchoalveolar lavage fluid indicate an exaggerated inflammatory response in pediatric cystic fibrosis patients. Clin Chem 53: 1782–1791.

38. VoglT, TenbrockK, LudwigS, LeukertN, EhrhardtC, et al. (2007) Mrp8 and Mrp14 are endogenous activators of toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med 13: 1042–1049.

39. PeschkeT, BenderA, NainM, GemsaD (1993) Role of macrophage cytokines in influenza A virus lnfections. Immunobiology 189: 340–355.

40. HeroldS, SteinmuellerM, von WulffenW, CakarovaL, PintoR, et al. (2008) Lung epithelial apoptosis in influenza virus pneumonia: The role of macrophage-expressed TNF-related apoptosis-inducing ligand. J Exp Med 205: 3065–3077.

41. HoeveMA, NashAA, JacksonD, RandallRE, DransfieldI (2012) Influenza virus A infection of human monocyte and macrophage subpopulations reveals increased susceptibility associated with cell differentiation. PLoS One 7: e29443.

42. HuangF, BarnesPF, FengY, DonisR, ChroneosZC, et al. (2011) GM-CSF in the lung protects against lethal influenza infection. Am J Respir Crit Care Med 184: 259–268.

43. ZhangZ, KimT, BaoM, FacchinettiV, JungS, et al. (2011) DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity 34: 866–878.

44. RyckmanC, VandalK, RouleauP, TalbotM, TessierPA (2003) Proinflammatory activities of S100: Proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. J Immunol 170: 3233–3242.

45. AncerizN, VandalK, TessierPA (2007) S100A9 mediates neutrophil adhesion to fibronectin through activation of β2 integrins. Biochem Biophys Res Commun 354: 84–89.

46. CesaroA, AncerizN, PlanteA, PageN, TardifMR, et al. (2012) An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis. PLoS One 7: e45478.

47. SimardJ, GirardD, TessierPA (2010) Induction of neutrophil degranulation by S100A9 via a MAPK-dependent mechanism. J Leukoc Biol 87: 905–914.

48. SimardJ, SimonM, TessierPA, GirardD (2011) Damage-associated molecular pattern S100A9 increases bactericidal activity of human neutrophils by enhancing phagocytosis. J Immunol 186: 3622–3631.

49. RaquilMA, AncerizN, RouleauP, TessierPA (2008) Blockade of antimicrobial proteins S100A8 and S100A9 inhibits phagocyte migration to the alveoli in streptococcal pneumonia. J Immunol 180: 3366–3374.

50. VandalK, RouleauP, BoivinA, RyckmanC, TalbotM, et al. (2003) Blockade of S100A8 and S100A9 suppresses neutrophil migration in response to lipopolysaccharide. J Immunol 171: 2602–2609.

51. AtallahM, KrispinA, TrahtembergU, Ben-HamronS, GrauA, et al. (2012) Constitutive neutrophil apoptosis: Regulation by cell concentration via S100 A8/9 and the MEK-ERK pathway. PLoS One 7: e29333.

52. GhavamiS, EshragiM, AndeSR, ChazinWJ, KlonischT, et al. (2010) S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3. Cell Res 20: 314–331.

53. LiC, ChenH, DingF, ZhangY, LuoA, et al. (2009) A novel p53 target gene, S100A9, induces p53-dependent cellular apoptosis and mediates the p53 apoptosis pathway. Biochem J 422: 363–372.

54. ViemannD, BarczykK, VoglT, FischerU, SunderkötterC, et al. (2007) MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program. Blood 109: 2453–2460.

55. SeeligerS, VoglT, EngelsIH, SchröderJM, SorgC, et al. (2003) Expression of calcium-binding proteins MRP8 and MRP14 in inflammatory muscle diseases. Am j pathol 163: 947–956.

56. YiH, PatelAK, SodhiCP, HackamDJ, HackamAS (2012) Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis. PLoS One 7: e36560.

57. EquilsO, LuD, GatterM, WitkinSS, BertolottoC, et al. (2006) Chlamydia heat shock protein 60 induces trophoblast apoptosis through TLR4. J Immunol 177: 1257–1263.

58. De TrezC, PajakB, BraitM, GlaichenhausN, UrbainJ, et al. (2005) TLR4 and toll-IL-1 receptor domain-containing adapter-Inducing IFN-β but not MyD88, regulate escherichia coli-induced dendritic cell maturation and apoptosis in vivo. J Immunol 175: 839–846.

59. BasakC, PathakSK, BhattacharyyaA, PathakS, BasuJ, et al. (2005) The secreted peptidyl prolyl cis,trans-isomerase HP0175 of helicobacter pylori induces apoptosis of gastric epithelial cells in a TLR4- and apoptosis signal-regulating kinase 1-dependent manner. J Immunol 174: 5672–5680.

60. NealMD, SodhiCP, JiaH, DyerM, EganCE, et al. (2012) Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis. J Biol Chem 287: 37296–37308.

61. SanchezD, RojasM, HernandezI, RadziochD, GarciaLF, et al. (2010) Role of TLR2- and TLR4-mediated signaling in mycobacterium tuberculosis-induced macrophage death. Cell Immunol 260: 128–136.

62. SuzukiT, KobayashiM, IsatsuK, NishiharaT, AiuchiT, et al. (2004) Mechanisms involved in apoptosis of human macrophages induced by lipopolysaccharide from actinobacillus actinomycetemcomitans in the presence of cycloheximide. Infect Immun 72: 1856–1865.

63. WelliverTP, GarofaloRP, HosakoteY, HintzKH, AvendanoL, et al. (2007) Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. J Infect Dis 195: 1126–1136.

64. HinshawVS, OlsenCW, Dybdahl-SissokoN, EvansD (1994) Apoptosis: A mechanism of cell killing by influenza A and B viruses. J Virol 68: 3667–3673.

65. ZhangC, YangY, ZhouX, LiuX, SongH, et al. (2010) Highly pathogenic avian influenza A virus H5N1 NS1 protein induces caspase-dependent apoptosis in human alveolar basal epithelial cells. Virol J 7: 51.

66. LuX, MasicA, LiY, ShinY, LiuQ, et al. (2010) The PI3K/Akt pathway inhibits influenza A virus-induced bax-mediated apoptosis by negatively regulating the JNK pathway via ASK1. J Gen Virol 91: 1439–1449.

67. BrydonEW, MorrisSJ, SweetC (2005) Role of apoptosis and cytokines in influenza virus morbidity. FEMS Microbiol Rev 29: 837–850.

68. VandivierRW, HensonPM, DouglasIS (2006) Burying the Dead*The impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease. CHEST 129: 1673–1682.

69. HermannA, DonatoR, WeigerTM, ChazinWJ (2012) S100 calcium binding proteins and ion channels. Front Pharmacol 3: 67.

70. HalaykoAJ, GhavamiS (2009) S100A8/A9: A mediator of severe asthma pathogenesis and morbidity? Can J Physiol Pharmacol 87: 743–755.

71. KimTH, ChowYH, GillSE, SchnappLM (2012) Effect of insulin-like growth factor blockade on hyperoxia-induced lung injury. Am J Respir Cell Mol Biol 47: 372–378.

72. ToewsGB, HartDA, HansenEJ (1985) Effect of systemic immunization on pulmonary clearance of haemophilus influenzae type b. Infect Immun 48: 343–349.

73. TeranLM, RuggebergS, SantiagoJ, Fuentes-ArenasF, HernandezJL, et al. (2012) Immune response to seasonal influenza A virus infection: A proteomic approach. Arch Med Res 43: 464–469.

74. EndohY, ChungYM, ClarkIA, GeczyCL, HsuK (2009) IL-10-dependent S100A8 gene induction in monocytes/macrophages by double-stranded RNA. J Immunol 182: 2258–2268.

75. MgbemenaV, SegoviaJA, ChangTH, TsaiSY, ColeGT, et al. (2012) Transactivation of inducible nitric oxide synthase gene by kruppel-like factor 6 regulates apoptosis during influenza A virus infection. J Immunol 189: 606–615.

76. AchouitiA, VoglT, UrbanCF, RöhmM, HommesTJ, et al. (2012) Myeloid-related protein-14 contributes to protective immunity in gram-negative pneumonia derived sepsis. PLoS Pathog 8: e1002987.

77. UebaO (1978) Respiratory syncytial virus. I. concentration and purification of the infectious virus. Acta Med Okayama 32: 265–272.

78. EchchgaddaI, ChangTH, SabbahA, BakriI, IkenoY, et al. (2011) Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus (RSV): Consequences of deficient interferon-dependent antiviral defense. BMC Cancer 11: 43.

79. EchchgaddaI, KotaS, DeLa CruzI, SabbahA, ChangT, et al. (2009) Anticancer oncolytic activity of respiratory syncytial virus. Cancer Gene Ther 16: 923–935.