Type I Interferon Protects against Pneumococcal Invasive Disease by Inhibiting Bacterial Transmigration across the Lung

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Streptococcus pneumoniae infection is a leading cause of bacterial pneumonia, sepsis and meningitis and is associated with high morbidity and mortality. Type I interferon (IFN-I), whose contribution to antiviral and intracellular bacterial immunity is well established, is also elicited during pneumococcal infection, yet its functional significance is not well defined. Here, we show that IFN-I plays an important role in the host defense against pneumococci by counteracting the transmigration of bacteria from the lung to the blood. Mice that lack the type I interferon receptor (Ifnar1^−/−) or mice that were treated with a neutralizing antibody against the type I interferon receptor, exhibited enhanced development of bacteremia following intranasal pneumococcal infection, while maintaining comparable bacterial numbers in the lung. In turn, treatment of mice with IFNβ or IFN-I-inducing synthetic double stranded RNA (poly(I:C)), dramatically reduced the development of bacteremia following intranasal infection with S. pneumoniae. IFNβ treatment led to upregulation of tight junction proteins and downregulation of the pneumococcal uptake receptor, platelet activating factor receptor (PAF receptor). In accordance with these findings, IFN-I reduced pneumococcal cell invasion and transmigration across epithelial and endothelial layers, and Ifnar1^−/− mice showed overall enhanced lung permeability. As such, our data identify IFN-I as an important component of the host immune defense that regulates two possible mechanisms involved in pneumococcal invasion, i.e. PAF receptor-mediated transcytosis and tight junction-dependent pericellular migration, ultimately limiting progression from a site-restricted lung infection to invasive, lethal disease.

Vyšlo v časopise: Type I Interferon Protects against Pneumococcal Invasive Disease by Inhibiting Bacterial Transmigration across the Lung. PLoS Pathog 9(11): e32767. doi:10.1371/journal.ppat.1003727
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003727

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Zdroje

1. AustrianR (1986) Some aspects of the pneumococcal carrier state. J Antimicrob Chemother 18 Suppl A: 35–45.

2. HogbergL, GeliP, RingbergH, MelanderE, LipsitchM, et al. (2007) Age- and serogroup-related differences in observed durations of nasopharyngeal carriage of penicillin-resistant pneumococci. J Clin Microbiol 45: 948–952.

3. MusherDM (1992) Infections caused by Streptococcus pneumoniae: clinical spectrum, pathogenesis, immunity, and treatment. Clin Infect Dis 14: 801–807.

4. O'BrienKL, WolfsonLJ, WattJP, HenkleE, Deloria-KnollM, et al. (2009) Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 374: 893–902.

5. McCullersJA, TuomanenEI (2001) Molecular pathogenesis of pneumococcal pneumonia. Front Biosci 6: D877–889.

6. PallaresR, LinaresJ, VadilloM, CabellosC, ManresaF, et al. (1995) Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med 333: 474–480.

7. SchuchatA, RobinsonK, WengerJD, HarrisonLH, FarleyM, et al. (1997) Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med 337: 970–976.

8. Mook-KanamoriBB, GeldhoffM, van der PollT, van de BeekD (2011) Pathogenesis and pathophysiology of pneumococcal meningitis. Clinical Microbiology Reviews 24: 557–591.

9. CundellDR, GerardNP, GerardC, Idanpaan-HeikkilaI, TuomanenEI (1995) Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377: 435–438.

10. Le GouillC, ParentJL, Rola-PleszczynskiM, StankovaJ (1997) Structural and functional requirements for agonist-induced internalization of the human platelet-activating factor receptor. J Biol Chem 272: 21289–21295.

11. RadinJN, OrihuelaCJ, MurtiG, GuglielmoC, MurrayPJ, et al. (2005) beta-Arrestin 1 participates in platelet-activating factor receptor-mediated endocytosis of Streptococcus pneumoniae. Infection and Immunity 73: 7827–7835.

12. RijneveldAW, WeijerS, FlorquinS, SpeelmanP, ShimizuT, et al. (2004) Improved host defense against pneumococcal pneumonia in platelet-activating factor receptor-deficient mice. Journal of Infectious Diseases 189: 711–716.

13. ClarkeTB, FrancellaN, HuegelA, WeiserJN (2011) Invasive bacterial pathogens exploit TLR-mediated downregulation of tight junction components to facilitate translocation across the epithelium. Cell Host Microbe 9: 404–414.

14. AttaliC, DurmortC, VernetT, Di GuilmiAM (2008) The interaction of Streptococcus pneumoniae with plasmin mediates transmigration across endothelial and epithelial monolayers by intercellular junction cleavage. Infection and Immunity 76: 5350–5356.

15. KolumamGA, ThomasS, ThompsonLJ, SprentJ, Murali-KrishnaK (2005) Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. J Exp Med 202: 637–650.

16. ToughDF, BorrowP, SprentJ (1996) Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272: 1947–1950.

17. ChoHJ, HayashiT, DattaSK, TakabayashiK, Van UdenJH, et al. (2002) IFN-alpha beta promote priming of antigen-specific CD8+ and CD4+ T lymphocytes by immunostimulatory DNA-based vaccines. J Immunol 168: 4907–4913.

18. AlsharifiM, LobigsM, RegnerM, LeeE, KoskinenA, et al. (2005) Type I interferons trigger systemic, partial lymphocyte activation in response to viral infection. J Immunol 175: 4635–4640.

19. TheofilopoulosAN, BaccalaR, BeutlerB, KonoDH (2005) Type I interferons (alpha/beta) in immunity and autoimmunity. Annu Rev Immunol 23: 307–336.

20. PestkaS, KrauseCD, WalterMR (2004) Interferons, interferon-like cytokines, and their receptors. Immunol Rev 202: 8–32.

21. AggarwalBB, PanditaR (1994) Both type I and type II interferons down-regulate human tumor necrosis factor receptors in human hepatocellular carcinoma cell line Hep G2. Role of protein kinase C. FEBS Lett 337: 99–102.

22. GuardaG, BraunM, StaehliF, TardivelA, MattmannC, et al. (2011) Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity 34: 213–223.

23. JoyceEA, PopperSJ, FalkowS (2009) Streptococcus pneumoniae nasopharyngeal colonization induces type I interferons and interferon-induced gene expression. BMC Genomics 10: 404.

24. ParkerD, MartinFJ, SoongG, HarfenistBS, AguilarJL, et al. (2011) Streptococcus pneumoniae DNA initiates type I interferon signaling in the respiratory tract. MBio 2: e00016–00011.

25. NakamuraS, DavisKM, WeiserJN (2011) Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice. Journal of Clinical Investigation 121: 3657–3665.

26. MancusoG, MidiriA, BiondoC, BeninatiC, ZummoS, et al. (2007) Type I IFN signaling is crucial for host resistance against different species of pathogenic bacteria. J Immunol 178: 3126–3133.

27. KoppeU, HognerK, DoehnJM, MullerHC, WitzenrathM, et al. (2012) Streptococcus pneumoniae stimulates a STING- and IFN regulatory factor 3-dependent type I IFN production in macrophages, which regulates RANTES production in macrophages, cocultured alveolar epithelial cells, and mouse lungs. Journal of Immunology 188: 811–817.

28. OrihuelaCJ, GaoG, McGeeM, YuJ, FrancisKP, et al. (2003) Organ-specific models of Streptococcus pneumoniae disease. Scand J Infect Dis 35: 647–652.

29. BeisswengerC, CoyneCB, ShchepetovM, WeiserJN (2007) Role of p38 MAP kinase and transforming growth factor-beta signaling in transepithelial migration of invasive bacterial pathogens. J Biol Chem 282: 28700–28708.

30. TalbotUM, PatonAW, PatonJC (1996) Uptake of Streptococcus pneumoniae by respiratory epithelial cells. Infection and Immunity 64: 3772–3777.

31. SunSC, GanchiPA, BallardDW, GreeneWC (1993) NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway. Science 259: 1912–1915.

32. BrownK, ParkS, KannoT, FranzosoG, SiebenlistU (1993) Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. Proc Natl Acad Sci U S A 90: 2532–2536.

33. ScottML, FujitaT, LiouHC, NolanGP, BaltimoreD (1993) The p65 subunit of NF-kappa B regulates I kappa B by two distinct mechanisms. Genes Dev 7: 1266–1276.

34. ShivshankarP, SanchezC, RoseLF, OrihuelaCJ (2009) The Streptococcus pneumoniae adhesin PsrP binds to Keratin 10 on lung cells. Molecular Microbiology 73: 663–679.

35. OrihuelaCJ, MahdaviJ, ThorntonJ, MannB, WooldridgeKG, et al. (2009) Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. Journal of Clinical Investigation 119: 1638–1646.

36. VossS, HallstromT, SalehM, BurchhardtG, PribylT, et al. (2013) The Choline-binding Protein PspC of Streptococcus pneumoniae Interacts with the C-terminal Heparin-binding Domain of Vitronectin. Journal of Biological Chemistry 288: 15614–15627.

37. AgarwalV, AsmatTM, LuoS, JenschI, ZipfelPF, et al. (2010) Complement regulator Factor H mediates a two-step uptake of Streptococcus pneumoniae by human cells. Journal of Biological Chemistry 285: 23486–23495.

38. HammerschmidtS, AgarwalV, KunertA, HaelbichS, SkerkaC, et al. (2007) The host immune regulator factor H interacts via two contact sites with the PspC protein of Streptococcus pneumoniae and mediates adhesion to host epithelial cells. Journal of Immunology 178: 5848–5858.

39. QuinLR, OnwubikoC, MooreQC, MillsMF, McDanielLS, et al. (2007) Factor H binding to PspC of Streptococcus pneumoniae increases adherence to human cell lines in vitro and enhances invasion of mouse lungs in vivo. Infection and Immunity 75: 4082–4087.

40. WagnerC, KhanAS, KamphausenT, SchmausserB, UnalC, et al. (2007) Collagen binding protein Mip enables Legionella pneumophila to transmigrate through a barrier of NCI-H292 lung epithelial cells and extracellular matrix. Cell Microbiol 9: 450–462.

41. AttaliC, DurmortC, VernetT, Di GuilmiAM (2008) The interaction of Streptococcus pneumoniae with plasmin mediates transmigration across endothelial and epithelial monolayers by intercellular junction cleavage. Infect Immun 76: 5350–5356.

42. SpeshockJL, Doyon-RealeN, RabahR, NeelyMN, RobertsPC (2007) Filamentous influenza A virus infection predisposes mice to fatal septicemia following superinfection with Streptococcus pneumoniae serotype 3. Infect Immun 75: 3102–3111.

43. KlugmanKP, ChienYW, MadhiSA (2009) Pneumococcal pneumonia and influenza: a deadly combination. Vaccine 27 Suppl 3: C9–C14.

44. O'BrienKL, WaltersMI, SellmanJ, QuinliskP, RegneryH, et al. (2000) Severe pneumococcal pneumonia in previously healthy children: the role of preceding influenza infection. Clin Infect Dis 30: 784–789.

45. StensballeLG, HjulerT, AndersenA, KaltoftM, RavnH, et al. (2008) Hospitalization for respiratory syncytial virus infection and invasive pneumococcal disease in Danish children aged <2 years: a population-based cohort study. Clin Infect Dis 46: 1165–1171.

46. KrausJ, LingAK, HammS, VoigtK, OschmannP, et al. (2004) Interferon-beta stabilizes barrier characteristics of brain endothelial cells in vitro. Annals of Neurology 56: 192–205.

47. MinagarA, LongA, MaT, JacksonTH, KelleyRE, et al. (2003) Interferon (IFN)-beta 1a and IFN-beta 1b block IFN-gamma-induced disintegration of endothelial junction integrity and barrier. Endothelium 10: 299–307.

48. KurugantiPA, HinojozaJR, EatonMJ, EhmannUK, SobelRA (2002) Interferon-beta counteracts inflammatory mediator-induced effects on brain endothelial cell tight junction molecules-implications for multiple sclerosis. Journal of Neuropathology and Experimental Neurology 61: 710–724.

49. KatakuraK, LeeJ, RachmilewitzD, LiG, EckmannL, et al. (2005) Toll-like receptor 9-induced type I IFN protects mice from experimental colitis. J Clin Invest 115: 695–702.

50. Vijay-KumarM, WuH, AitkenJ, KolachalaVL, NeishAS, et al. (2007) Activation of toll-like receptor 3 protects against DSS-induced acute colitis. Inflamm Bowel Dis 13: 856–864.

51. BukholmG, BerdalBP, HaugC, DegreM (1984) Mouse fibroblast interferon modifies Salmonella typhimurium infection in infant mice. Infect Immun 45: 62–66.

52. NieselDW, HessCB, ChoYJ, KlimpelKD, KlimpelGR (1986) Natural and recombinant interferons inhibit epithelial cell invasion by Shigella spp. Infect Immun 52: 828–833.

53. WeigentDA, HuffTL, PetersonJW, StantonGJ, BaronS (1986) Role of interferon in streptococcal infection in the mouse. Microb Pathog 1: 399–407.

54. ShahangianA, ChowEK, TianX, KangJR, GhaffariA, et al. (2009) Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice. J Clin Invest 119: 1910–1920.

55. KnappS, LeemansJC, FlorquinS, BrangerJ, MarisNA, et al. (2003) Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia. American Journal of Respiratory and Critical Care Medicine 167: 171–179.

56. FillonS, SoulisK, RajasekaranS, Benedict-HamiltonH, RadinJN, et al. (2006) Platelet-activating factor receptor and innate immunity: uptake of gram-positive bacterial cell wall into host cells and cell-specific pathophysiology. J Immunol 177: 6182–6191.

57. KeelyS, GloverLE, WeissmuellerT, MacManusCF, FillonS, et al. (2010) Hypoxia-inducible factor-dependent regulation of platelet-activating factor receptor as a route for gram-positive bacterial translocation across epithelia. Mol Biol Cell 21: 538–546.

58. PrescottSM, ZimmermanGA, StafforiniDM, McIntyreTM (2000) Platelet-activating factor and related lipid mediators. Annual Review of Biochemistry 69: 419–445.

59. EdwardsLJ, ConstantinescuCS (2009) Platelet activating factor/platelet activating factor receptor pathway as a potential therapeutic target in autoimmune diseases. Inflamm Allergy Drug Targets 8: 182–190.

60. TsouprasAB, IatrouC, FrangiaC, DemopoulosCA (2009) The implication of platelet activating factor in cancer growth and metastasis: potent beneficial role of PAF-inhibitors and antioxidants. Infect Disord Drug Targets 9: 390–399.

61. HsuehW, CaplanMS, SunX, TanX, MacKendrickW, et al. (1994) Platelet-activating factor, tumor necrosis factor, hypoxia and necrotizing enterocolitis. Acta Paediatr Suppl 396: 11–17.

62. XuLF, TengX, GuoJ, SunM (2012) Protective effect of intestinal trefoil factor on injury of intestinal epithelial tight junction induced by platelet activating factor. Inflammation 35: 308–315.

63. McCullersJA, IversonAR, McKeonR, MurrayPJ (2008) The platelet activating factor receptor is not required for exacerbation of bacterial pneumonia following influenza. Scandinavian Journal of Infectious Diseases 40: 11–17.

64. LacksS, HotchkissRD (1960) A study of the genetic material determining an enzyme in Pneumococcus. Biochim Biophys Acta 39: 508–518.

65. BlasigIE, GieseH, SchroeterML, SporbertA, UtepbergenovDI, et al. (2001) *NO and oxyradical metabolism in new cell lines of rat brain capillary endothelial cells forming the blood-brain barrier. Microvasc Res 62: 114–127.

66. MullerU, SteinhoffU, ReisLF, HemmiS, PavlovicJ, et al. (1994) Functional role of type I and type II interferons in antiviral defense. Science 264: 1918–1921.

67. MausUA, SrivastavaM, PatonJC, MackM, EverhartMB, et al. (2004) Pneumolysin-induced lung injury is independent of leukocyte trafficking into the alveolar space. Journal of Immunology 173: 1307–1312.

68. TalbotUM, PatonAW, PatonJC (1996) Uptake of Streptococcus pneumoniae by respiratory epithelial cells. Infect Immun 64: 3772–3777.

69. GriggJ, WaltersH, SohalSS, Wood-BakerR, ReidDW, et al. (2012) Cigarette smoke and platelet-activating factor receptor dependent adhesion of Streptococcus pneumoniae to lower airway cells. Thorax 67: 908–913.

70. van der SluijsKF, van EldenLJ, NijhuisM, SchuurmanR, FlorquinS, et al. (2006) Involvement of the platelet-activating factor receptor in host defense against Streptococcus pneumoniae during postinfluenza pneumonia. Am J Physiol Lung Cell Mol Physiol 290: L194–199.

71. SheahanS, BellamyCO, HarlandSN, HarrisonDJ, ProstS (2008) TGFbeta induces apoptosis and EMT in primary mouse hepatocytes independently of p53, p21Cip1 or Rb status. BMC Cancer 8: 191.

72. SongHL, LvS, LiuP (2009) The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure. BMC Gastroenterol 9: 70.

73. KawaiY, HamazakiY, FujitaH, FujitaA, SatoT, et al. (2011) Claudin-4 induction by E-protein activity in later stages of CD4/8 double-positive thymocytes to increase positive selection efficiency. Proceedings of the National Academy of Sciences of the United States of America 108: 4075–4080.