IL-1α and Complement Cooperate in Triggering Local Neutrophilic Inflammation in Response to Adenovirus and Eliminating Virus-Containing Cells

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Adenovirus (Ad) induces a potent activation of pro-inflammatory cytokines and chemokines upon interaction with tissue macrophages in vivo. However, critical factors affecting cellular inflammatory responses to Ad and their functional significance remain unclear. Here we show that in the model of disseminated infection, intravenous Ad administration leads to a rapid release of pro-inflammatory Ly-6G+7/4+ leukocytes (PMNs) from the bone marrow into the blood. PMNs enter into peripheral tissues and, in the case of spleen, are accumulated in proximity to the virus-containing MARCO+ macrophages within the splenic marginal zone (MZ). Mechanistic dissection of molecular queues that guide PMN migration reveals that CXCL1 and CXCL2 chemokines are only partially responsible for CXCR2-dependent PMN recruitment into the splenic MZ. We further found that complement cooperates with IL-1α-IL-1RI-CXCR2 signaling pathways in recruitment of PMNs to the splenic MZ, which results in elimination of virus-containing MARCO+ macrophages from the spleen. Administration of complement-blocking CR2-Crry or CR2-fH proteins into IL-1α-deficient, but not wild-type, mice prevents PMN accumulation in the splenic MZ and elimination of virus-containing macrophages from the spleen. Our study defines the functional significance of molecular and cellular host defense mechanisms that cooperate in eliminating virus-containing cells in the model of acute disseminated Ad infection.

Vyšlo v časopise: IL-1α and Complement Cooperate in Triggering Local Neutrophilic Inflammation in Response to Adenovirus and Eliminating Virus-Containing Cells. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004035
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004035

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1. KhareR, ChenCY, WeaverEA, BarryMA (2011) Advances and future challenges in adenoviral vector pharmacology and targeting. Curr Gene Ther 11 : 241–258.

2. YamamotoM, CurielDT (2010) Current issues and future directions of oncolytic adenoviruses. Mol Ther 18 : 243–250.

3. MorralN, O'NealWK, RiceK, LelandMM, PiedraPA, et al. (2002) Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons. Hum Gene Ther 13 : 143–154.

4. Brunetti-PierriN, PalmerDJ, BeaudetAL, CareyKD, FinegoldM, et al. (2004) Acute toxicity after high-dose systemic injection of helper-dependent adenoviral vectors into nonhuman primates. Hum Gene Ther 15 : 35–46.

5. RaperSE, ChirmuleN, LeeFS, WivelNA, BaggA, et al. (2003) Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab 80 : 148–158.

6. RaperSE, YudkoffM, ChirmuleN, GaoGP, NunesF, et al. (2002) A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Hum Gene Ther 13 : 163–175.

7. LieberA, HeCY, MeuseL, SchowalterD, KirillovaI, et al. (1997) The role of Kupffer cell activation and viral gene expression in early liver toxicity after infusion of recombinant adenovirus vectors. J Virol 71 : 8798–8807.

8. ShayakhmetovDM, LiZY, NiS, LieberA (2004) Analysis of adenovirus sequestration in the liver, transduction of hepatic cells, and innate toxicity after injection of fiber-modified vectors. J Virol 78 : 5368–5381.

9. SmithJS, TianJ, LozierJN, ByrnesAP (2004) Severe pulmonary pathology after intravenous administration of adenovirus vectors in cirrhotic rats. Molecular Therapy 9 : 932–941.

10. Di PaoloNC, MiaoEA, IwakuraY, Murali-KrishnaK, AderemA, et al. (2009) Virus binding to a plasma membrane receptor triggers interleukin-1α-mediated proinflammatory macrophage response in vivo. Immunity 31 : 110–121.

11. ZaissAK, LiuQ, BowenGP, WongNC, BartlettJS, et al. (2002) Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors. J Virol 76 : 4580–4590.

12. Leruez-VilleM, MinardV, LacailleF, BuzynA, AbachinE, et al. (2004) Real-time blood plasma polymerase chain reaction for management of disseminated adenovirus infection. Clinical Infectious Diseases 38 : 45–52.

13. ArdehaliH, VolmarK, RobertsC, FormanM, BeckerLC (2001) Fatal disseminated adenoviral infection in a renal transplant patient. Transplantation 71 : 998–999.

14. LeenAM, RooneyCM (2005) Adenovirus as an emerging pathogen in immunocompromised patients. British Journal of Haematology 128 : 135–144.

15. KimYJ, BoeckhM, EnglundJA (2007) Community respiratory virus infections in immunocompromised patients: Hematopoletic stem cell and solid organ transplant recipients, and individuals with human immunodeficiency virus infection. Seminars in Respiratory and Critical Care Medicine 28 : 222–242.

16. LynchJP, FishbeinM, EchavarriaM (2011) Adenovirus. Seminars in Respiratory and Critical Care Medicine 32 : 494–511.

17. MuruveDA, BarnesMJ, StillmanIE, LibermannTA (1999) Adenoviral gene therapy leads to rapid induction of multiple chemokines and acute neutrophil-dependent hepatic injury in vivo. Hum Gene Ther 10 : 965–976.

18. MuruveDA (2004) The innate immune response to adenovirus vectors. Hum Gene Ther 15 : 1157–1166.

19. KolaczkowskaE, KubesP (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13 : 159–175.

20. MurrayPJ, WynnTA (2011) Protective and pathogenic functions of macrophage subsets. Nature Reviews Immunology 11 : 723–737.

21. LiY, MuruveDA, CollinsRG, LeeSS, KubesP (2002) The role of selectins and integrins in adenovirus vector-induced neutrophil recruitment to the liver. Eur J Immunol 32 : 3443–3452.

22. CotterMJ, MuruveDA (2006) Isolation of neutrophils from mouse liver: A novel method to study effector leukocytes during inflammation. Journal of Immunological Methods 312 : 68–78.

23. CestaMF (2006) Normal structure, function, and histology of mucosa-associated lymphoid tissue. Toxicologic Pathology 34 : 599–608.

24. ElmoreSA (2006) Enhanced histopathology of the spleen. Toxicologic Pathology 34 : 648–655.

25. CysterJG (2003) Lymphoid organ development and cell migration. Immunological Reviews 195 : 5–14.

26. HendrixCW, FlexnerC, MacFarlandRT, GiandomenicoC, FuchsEJ, et al. (2000) Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrobial Agents and Chemotherapy 44 : 1667–1673.

27. GouwyM, StruyfS, CatusseJ, ProostP, Van DammeJ (2004) Synergy between proinflammatory ligands of G protein-coupled receptors in neutrophil activation and migration. Journal of Leukocyte Biology 76 : 185–194.

28. DaleDC, BolyardAA, KelleyML, WestrupEC, MakaryanV, et al. (2011) The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome. Blood 118 : 4963–4966.

29. BonigH, ChudziakD, PriestleyG, PapayannopoulouT (2009) Insights into the biology of mobilized hematopoietic stem/progenitor cells through innovative treatment schedules of the CXCR4 antagonist AMD3100. Experimental Hematology 37 : 402–415.

30. LukacsNW, BerlinA, ScholsD, SkerljRT, BridgerGJ (2002) AMD3100, a CxCR4 antagonist, attenuates allergic lung inflammation and airway Hyperreactivity. American Journal of Pathology 160 : 1353–1360.

31. Di PaoloNC, ShayakhmetovDM (2014) The analysis of innate immune response to adenovirus using antibody arrays. Methods Mol Biol 1089 : 133–141.

32. ShayakhmetovDM, LiZY, NiSH, LieberA (2005) Interference with the IL-1-signaling pathway improves the toxicity profile of systemically applied adenovirus vectors. Journal of Immunology 174 : 7310–7319.

33. GreberUF, WillettsM, WebsterP, HeleniusA (1993) Stepwise dismantling of adenovirus 2 during entry into cells. Cell 75 : 477–486.

34. GreberUF, WebsterP, WeberJ, HeleniusA (1996) The role of the adenovirus protease on virus entry into cells. Embo J 15 : 1766–1777.

35. ChenCJ, KonoH, GolenbockD, ReedG, AkiraS, et al. (2007) Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nature Medicine 13 : 851–856.

36. Di PaoloNC, ShayakhmetovDM (2013) Interleukin-1 receptor 2 keeps the lid on interleukin-1alpha. Immunity 38 : 203–205.

37. ZhengY, HumphryM, MaguireJJ, BennettMR, ClarkeMC (2013) Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1α, controlling necrosis-induced sterile inflammation. Immunity 38 : 285–295.

38. DinarelloCA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27 : 519–550.

39. DinarelloCA (2011) Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117 : 3720–3732.

40. McDonaldB, KubesP (2011) Cellular and molecular choreography of neutrophil recruitment to sites of sterile inflammation. J Mol Med (Berl) 89 : 1079–1088.

41. SilvaMT (2010) When two is better than one: macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system. J Leukoc Biol 87 : 93–106.

42. Di PaoloNC, DoroninK, BaldwinLK, PapayannopoulouT, ShayakhmetovDM (2013) The Transcription Factor IRF3 Triggers “Defensive Suicide” Necrosis in Response to Viral and Bacterial Pathogens. Cell Reports 3 : 1840–1846.

43. TingJPY, WillinghamSB, BergstralhDT (2008) NLRs at the intersection of cell death and immunity. Nature Reviews Immunology 8 : 372–379.

44. GalluzziL, VitaleI, AbramsJM, AlnemriES, BaehreckeEH, et al. (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death and Differentiation 19 : 107–120.

45. SmithJS, XuZL, TianJ, StevensonSC, ByrnesAP (2008) Interaction of systemically delivered adenovirus vectors with Kupffer cells in mouse liver. Human Gene Therapy 19 : 547–554.

46. ManickanE, SmithJS, TianJ, EggermanTL, LozierJN, et al. (2006) Rapid Kupffer cell death after intravenous injection of adenovirus vectors. Molecular Therapy 13 : 108–117.

47. TianJ, XuZL, SmithJS, HofherrSE, BarryMA, et al. (2009) Adenovirus Activates Complement by Distinctly Different Mechanisms In Vitro and In Vivo: Indirect Complement Activation by Virions In Vivo. Journal of Virology 83 : 5648–5658.

48. AtkinsonC, HeSQ, MorrisK, QiaoF, CaseyS, et al. (2010) Targeted Complement Inhibitors Protect against Posttransplant Cardiac Ischemia and Reperfusion Injury and Reveal an Important Role for the Alternative Pathway of Complement Activation. Journal of Immunology 185 : 7007–7013.

49. AtkinsonC, SongHB, LuB, QiaoF, BurnsTA, et al. (2005) Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection. Journal of Clinical Investigation 115 : 2444–2453.

50. HuangYX, QiaoF, AtkinsonC, HolersVM, TomlinsonS (2008) A Novel Targeted Inhibitor of the Alternative Pathway of Complement and Its Therapeutic Application in Ischemia/Reperfusion Injury. Journal of Immunology 181 : 8068–8076.

51. JiangH, WangZ, SerraD, FrankMM, AmalfitanoA (2004) Recombinant adenovirus vectors activate the alternative complement pathway, leading to the binding of human complement protein C3 independent of anti-Ad antibodies. Molecular Therapy 10 : 1140–1142.

52. KiangA, HartmanZC, EverettRS, SerraD, JiangHX, et al. (2006) Multiple innate inflammatory responses induced after systemic adenovirus vector delivery depend on a functional complement system. Molecular Therapy 14 : 588–598.

53. XuZL, SmithJS, TianJ, ByrnesAP (2010) Induction of Shock After Intravenous Injection of Adenovirus Vectors: A Critical Role for Platelet-activating Factor. Molecular Therapy 18 : 609–616.

54. MartineauAR, NewtonSM, WilkinsonKA, KampmannB, HallBM, et al. (2007) Neutrophil-mediated innate immune resistance to mycobacteria. Journal of Clinical Investigation 117 : 1988–1994.

55. SharmaS, VermaI, KhullerGK (2000) Antibacterial activity of human neutrophil peptide-1 against Mycobacterium tuberculosis H37RV: in vitro and ex vivo study. European Respiratory Journal 16 : 112–117.

56. AllenC, ThorntonP, DenesA, McCollBW, PierozynskiA, et al. (2012) Neutrophil Cerebrovascular Transmigration Triggers Rapid Neurotoxicity through Release of Proteases Associated with Decondensed DNA. Journal of Immunology 189 : 381–392.

57. DoroninK, FlattJW, Di PaoloNC, KhareR, KalyuzhniyO, et al. (2012) Coagulation factor X activates innate immunity to human species C adenovirus. Science 338 : 795–798.

58. AlbaR, BradshawAC, CoughlanL, DenbyL, McDonaldRA, et al. (2010) Biodistribution and retargeting of FX-binding ablated adenovirus serotype 5 vectors. Blood 116 : 2656–2664.

59. CoughlanL, BradshawAC, ParkerAL, RobinsonH, WhiteK, et al. (2012) Ad5:Ad48 hexon hypervariable region substitutions lead to toxicity and increased inflammatory responses following intravenous delivery. Mol Ther 20 : 2268–2281.

60. BelousovaN, MikheevaG, XiongC, SoghomonianS, YoungD, et al. (2010) Development of a targeted gene vector platform based on simian adenovirus serotype 24. J Virol 84 : 10087–10101.

61. SharmaA, BangariDS, TandonM, PandeyA, HogenEschH, et al. (2009) Comparative analysis of vector biodistribution, persistence and gene expression following intravenous delivery of bovine, porcine and human adenoviral vectors in a mouse model. Virology 386 : 44–54.

62. HofherrSE, AdamsKE, ChenCY, MayS, WeaverEA, et al. (2011) Real-time dynamic imaging of virus distribution in vivo. PLoS One 6: e17076.

63. GautierEL, ShayT, MillerJ, GreterM, JakubzickC, et al. (2012) Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol 13 : 1118–1128.

64. MovitaD, KreefftK, BiestaP, van OudenarenA, LeenenPJ, et al. (2012) Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages. J Leukoc Biol 92 : 723–733.

65. MorrisseyRE, HorvathC, SnyderEA, PatrickJ, MacDonaldJS (2002) Rodent Nonclinical safety evaluation studies of SCH 58500, an adenoviral vector for the p53 gene. Toxicological Sciences 65 : 266–275.

66. HofherrSE, MokH, GushikenFC, LopezJA, BarryMA (2007) Polyethylene glycol modification of adenovirus reduces platelet activation, endothelial cell activation, and thrombocytopenia. Human Gene Therapy 18 : 837–848.

67. StoneD, LiuY, ShayakhmetovD, LiZY, NiSH, et al. (2007) Adenovirus-platelet interaction in blood causes virus sequestration to the reticuloendothelial system of the liver. Journal of Virology 81 : 4866–4871.

68. DinarelloCA, SimonA, van der MeerJWM (2012) Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nature Reviews Drug Discovery 11 : 633–652.

69. DinarelloCA (2004) Therapeutic strategies to reduce IL-1 activity in treating local and systemic inflammation. Current Opinion in Pharmacology 4 : 378–385.

70. HoraiR, AsanoM, SudoK, KanukaH, SuzukiM, et al. (1998) Production of mice deficient in genes for interleukin (IL)-1α, IL-1β, IL-1α/β, and IL-1 receptor antagonist shows that IL-1 beta is crucial in turpentine-induced fever development and glucocorticoid secretion. Journal of Experimental Medicine 187 : 1463–1475.

71. ShornickLP, DeTogniP, MariathasanS, GoellnerJ, StraussSchoenbergerJ, et al. (1996) Mice deficient in IL-1β manifest impaired contact hypersensitivity to trinitrochlorobenzene. Journal of Experimental Medicine 183 : 1427–1436.

72. ShayakhmetovDM, LieberA (2000) Dependence of adenovirus infectivity on length of the fiber shaft domain. J Virol 74 : 10274–10286.

73. ShayakhmetovDM, PapayannopoulouT, StamatoyannopoulosG, LieberA (2000) Efficient gene transfer into human CD34(+) cells by a retargeted adenovirus vector. J Virol 74 : 2567–2583.

74. CiavarraRP, StephensA, NagyS, SekellickM, SteelC (2006) Evaluation of immunological paradigms in a virus model: Are dendritic cells critical for antiviral immunity and viral clearance? Journal of Immunology 177 : 492–500.