Mast Cells Expedite Control of Pulmonary Murine Cytomegalovirus Infection by Enhancing the Recruitment of Protective CD8 T Cells to the Lungs

English version České info

Being strategically located beneath endothelial and epithelial surfaces, mast cells (MC) serve as sentinels for invading pathogens at host-environment boundaries as part of the innate defense against infection. Host genetic resistance against cytomegaloviruses (CMV) is largely determined by the innate immune response, but an implication of MC in the adaptive immune defense against CMV has not been considered so far and is almost impossible to address in human infection. Using murine CMV as a model that in the past has already pioneered the discovery of fundamental principles in CMV-host interactions, our data reveal MC as central part of a novel crosstalk-axis between the innate and adaptive immune response to CMV. We found that upon host infection MC become rapidly activated and promote the recruitment of protective CD8 T cells to the lungs, a noted critical site of CMV pathogenesis in humans as well as in the mouse model. Enhanced tissue infiltration of CD8 T cells results in a reduced peak viral load and a faster clearance of productive infection. Realizing the importance of MC in the control of pulmonary CMV infection may help to develop new strategies for preventing CMV pneumonia by MC supplementation in recipients of hematopoietic cell transplantation.

Vyšlo v časopise: Mast Cells Expedite Control of Pulmonary Murine Cytomegalovirus Infection by Enhancing the Recruitment of Protective CD8 T Cells to the Lungs. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004100
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004100

Souhrn

Zdroje

1. HebartH, EinseleH (2004) Clinical aspects of CMV infection after stem cell transplantation. Human Immunol 65: 432–436.

2. Seo S, Boeckh M (2013) Clinical cytomegalovirus research: haematopoietic cell transplantation. In: Reddehase MJ, editor. Cytomegaloviruses: from molecular pathogenesis to intervention. Caister Academic Press, Norfolk, UK. Vol. II: pp337–353.

3. MayerA, PodlechJ, KurzS, SteffensHP, MaibergerS, et al. (1997) Bone marrow failure by cytomegalovirus is associated with an in vivo deficiency in the expression of essential stromal hemopoietin genes. J Virol 71: 4589–4598.

4. SteffensHP, PodlechJ, KurzS, AngeleP, DreisD, et al. (1998) Cytomegalovirus inhibits the engraftment of donor bone marrow cells by downregulation of hemopoietin gene expression in recipient stroma. J Virol 72: 5006–5015.

5. Holtappels R, Ebert S, Podlech J, Fink A, Böhm V, et al. (2013) Murine model for cytoimmuntherapy of CMV disease after haematopoietic cell transplantation. In: Reddehase MJ, editor. Cytomegaloviruses: from molecular pathogenesis to intervention. Caister Academic Press, Norfolk, UK. Vol. II: pp354–381.

6. QuabeckK (1994) The lung as a critical organ in marrow transplantation. Bone Marrow Transplant 14: 19–28.

7. LjungmanP (1995) Cytomegalovirus pneumonia: presentation, diagnosis, and treatment. Semin Respir Infect 10: 209–215.

8. RiddellSR (1995) Pathogenesis of cytomegalovirus pneumonia in immunocompromised hosts. Semin Respir Infect 10: 199–208.

9. ReddehaseMJ, WeilandF, MünchK, JonjicS, LüskeA, et al. (1985) Interstitial murine cytomegalovirus pneumonia after irradiation: characterization of cells that limit viral replication during established infection of the lungs. J Virol 55: 264–273.

10. HoltappelsR, PodlechJ, GeginatG, SteffensHP, ThomasD, et al. (1998) Control of murine cytomegalovirus in the lungs: relative but not absolute immunodominance of the immediate-early 1 nonapeptide during the antiviral cytolytic T-lymphocyte response in pulmonary infiltrates. J Virol 72: 7201–7212.

11. PodlechJ, HoltappelsR, Pahl-SeibertMF, SteffensHP, ReddehaseMJ (2000) Murine model of interstitial cytomegalovirus pneumonia in syngeneic bone marrow transplantation: persistence of protective pulmonary CD8-T-cell infiltrates after clearance of acute infection. J Virol 74: 7496–7507.

12. BalthesenM, MesserleM, ReddehaseMJ (1993) Lungs are a major organ site of cytomegalovirus latency and recurrence. J Virol 67: 5360–5366.

13. KurzS, SteffensHP, MayerA, HarrisJR, ReddehaseMJ (1997) Latency versus persistence or intermittent recurrences: evidence for a latent state of murine cytomegalovirus in the lungs. J Virol 71: 2980–2987.

14. KurzSK, ReddehaseMJ (1999) Patchwork pattern of transcriptional reactivation in the lungs indicates sequential checkpoints in the transition from murine cytomegalovirus latency to recurrence. J Virol 73: 8612–8622.

15. PodlechJ, HoltappelsR, WirtzN, SteffensHP, ReddehaseMJ (1998) Reconstitution of CD8 T cells is essential for the prevention of multiple-organ cytomegalovirus histopathology after bone marrow transplantation. J Gen Virol 79: 2099–2104.

16. Seckert CK, Grießl M, Büttner JK, Freitag K, Lemmermann NA, et al. (2013) Immune surveillance of cytomegalovirus latency and reactivation in murine models: link to ‘Memory Inflation’. In: Reddehase MJ, editor. Cytomegaloviruses: from molecular pathogenesis to intervention. Caister Academic Press, Norfolk, UK. Vol. I: pp374–416.

17. Alterio de GossM, HoltappelsR, SteffensHP, PodlechJ, AngeleP, et al. (1998) Control of cytomegalovirus in bone marrow transplantation chimeras lacking the prevailing antigen-presenting molecule in recipient tissues rests primarily on recipient-derived CD8 T cells. J Virol 72: 7733–7744.

18. SacherT, PodlechJ, MohrCA, JordanS, RuzsicsZ, et al. (2008) The major virus-producing cell type during murine cytomegalovirus infection, the hepatocyte, is not the source of virus dissemination in the host. Cell Host Microbe 3: 263–272.

19. StahlFR, HellerK, HalleS, KeyserKA, BuscheA, et al. (2013) Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung. PLoS Pathog 9: e1003828.

20. BöhmV, PodlechJ, ThomasD, DeegenP, Pahl-SeibertMF, et al. (2008) Epitope-specific in vivo protection against cytomegalovirus disease by CD8 T cells in the murine model of preemptive immunotherapy. Med Microbiol Immunol 197: 135–144.

21. ReddehaseMJ, RothbardJB, KoszinowskiUH (1989) A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes. Nature 337: 651–653.

22. SimonCO, HoltappelsR, TervoHM, BöhmV, DäubnerT, et al. (2006) CD8 T cells control cytomegalovirus latency by epitope-specific sensing of transcriptional reactivation. J Virol 80: 10436–10456.

23. ReddehaseMJ, KoszinowskiUH (1991) Redistribution of critical major histocompatibility complex and T cell receptor-binding functions of residues in an antigenic sequence after biterminal substitution. Eur J Immunol 21: 1697–1701.

24. LemmermannNA, GergelyK, BöhmV, DeegenP, DäubnerT, et al. (2010) Immune evasion proteins of murine cytomegalovirus preferentially affect cell surface display of recently generated peptide presentation complexes. J Virol 84: 1221–1236.

25. LemmermannNA, KroppKA, SeckertCK, GrzimekNK, ReddehaseMJ (2011) Reverse genetics modification of cytomegalovirus antigenicity and immunogenicity by CD8 T-cell epitope deletion and insertion. J Biomed Biotechnol 2011: 812742.

26. SacherT, AndrassyJ, KalninsA, DölkenL, JordanS, et al. (2011) Shedding light on the elusive role of endothelia cells in cytomegalovirus dissemination. PLoS Pathog 7: e1002366.

27. GalkinaE, ThatteJ, DabakV, WilliamsMB, LeyK, et al. (2005) Preferential migration of effector CD8+ T cells into the interstitium of the normal lung. J Clin Invest 115: 3473–3483.

28. ZlotnikA, YoshieO (2000) Chemokines: a new classification system and their role in immunity. Immunity 12: 121–127.

29. McAlpineSM, IssekutzTB, MarshallJS (2012) Virus stimulation of human mast cells results in the recruitment of CD56+ T cells by a mechanism dependent on CCR5 ligands. FASEB J 26: 1280–1289.

30. OrinskaZ, BulanovaE, BudagianV, MetzM, MaurerM, et al. (2005) TLR3-induced activation of mast cells modulates CD8+ T-cell recruitment. Blood 106: 978–987.

31. RodewaldHR, FeyerabendTB (2012) Widespread immunological functions of mast cells: fact or fiction? Immunity 37: 13–24.

32. MatsushimaH, YamadaN, MatsueH, ShimadaS (2004) TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells. J Immunol 173: 531–541.

33. KulkaM, MetcalfeDD (2006) TLR3 activation inhibits human mast cell attachment to fibronectin and vitronectin. Mol Immunol 43: 1579–1586.

34. SandigH, Bulfone-PausS (2012) TLR signaling in mast cells: common and unique features. Front Immunol 3: 185 doi:10.3389/fimmu.2012.00185

35. LyonMF, GlenisterPH (1982) A new allele sash (Wsh) at the W-locus and a spontaneous recessive lethal in mice. Genet Res 39: 315–322.

36. GrimbaldestonMA, ChenCC, PiliponskyAM, TsaiM, TamSY, et al. (2005) Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo. Am J Pathol 167: 835–848.

37. WoltersPJ, Mallen-St ClairJ, LewisCC, VillaltaSA, BalukP, et al. (2005) Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient Kit(W-sh)/Kit(W-sh) sash mice. Clin Exp Allergy 35: 82–88.

38. AnguloA, GhazalP, MesserleM (2000) The major immediate-early gene ie3 of mouse cytomegalovirus is essential for viral growth. J Virol 74: 11129–11136.

39. JonjicS, MutterW, WeilandF, ReddehaseMJ, KoszinowskiUH (1989) Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes. J Exp Med 169: 1199–1212.

40. CampbellAE, CavanaughVJ, SlaterJS (2008) The salivary glands as a privileged site of cytomegalovirus immune evasion and persistence. Med Microbiol Immunol 197: 205–213.

41. AraseH, MocarskiES, CampbellAE, HillAB, LanierLL (2002) Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296: 1323–1326.

42. SmithHRC, HeuselJW, MehtaIK, KimS, DornerBG, et al. (2002) Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci USA 99: 8826–8831.

43. MitrovicM, ArapovicJ, JordanS, Fodil-CornuN, EbertS, et al. (2012) The NK cell response to mouse cytomegalovirus infection affects the level and kinetics of the early CD8(+) T-cell response. J Virol 86: 2165–2175.

44. WalzerT, BléryM, ChaixJ, FuseriN, ChassonL, et al. (2007) Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46. Proc Natl Acad Sci USA 104: 3384–3389.

45. BubicI, WagnerM, KrmpoticA, SauligT, KimS, et al. (2004) Gain of virulence caused by loss of a gene in murine cytomegalovirus. J Virol 78: 7536–7544.

46. AndersonKG, SungH, SkonCN, LefrancoisL, DeisingerA, et al. (2012) Cutting edge: intravascular staining redefines lung CD8 T cell responses. J Immunol 189: 2702–2706.

47. JarvisMA, NelsonJA (2007) Human cytomegalovirus tropism for endothelial cells: not all endothelial cells are created equal. J Virol 81: 2095–2101.

48. AbrahamSN, St JohnAL (2010) Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol 10: 440–452.

49. MunksMW, ChoKS, PintoAK, SierroS, KlenermanP, et al. (2006) Four distinct patterns of memory CD8 T cell responses to chronic murine cytomegalovirus infection. J Immunol 177: 450–458.

50. GibbonsAE, PriceP, RobertsonTA, PapadimitriouJM, ShellamGR (1990) Replication of murine cytomegalovirus in mast cells. Arch Virol 115: 299–307.

51. WagnerFM, BrizicI, PragerA, TrsanT, ArapovicM, et al. (2013) The viral chemokine MCK-2 of murine cytomegalovirus promotes infection as part of a gH/gL/MCK-2 complex. PLoS Pathog 9: e1003493.

52. MunksMW, GoldMC, ZajacAL, DoomCM, MorelloCS, et al. (2006) Genome-wide analysis reveals a highly diverse CD8 T cell response to murine cytomegalovirus. J Immunol 176: 3760–3766.

53. LemmermannNA, BöhmV, HoltappelsR, ReddehaseMJ (2011) In vivo impact of cytomegalovirus evasion of CD8 T-cell immunity: facts and thoughts based on murine models. Virus Res 157: 161–174.

54. LemmermannNA, FinkA, PodlechJ, EbertS, WilhelmiV, et al. (2012) Murine cytomegalovirus immune evasion proteins operative in the MHC class I pathway of antigen processing and presentation: state of knowledge, revisions, and questions. Med Microbiol Immunol 201: 497–512.

55. ThimmeR, AppayV, KoschellaM, PantherE, RothE, et al. (2005) Increased expression of the NK cell receptor KLRG1 by virus-specific CD8 T cells during persistent antigen stimulation. J Virol 79: 12112–12116.

56. ObarJJ, LefrançoisL (2010) Memory CD8+ T cell differentiation. Ann NY Acad Sci 1183: 251–266.

57. TsaiM, GalliSJ (2012) IgE and mast cells in allergic disease. Nat Med 18: 693–704.

58. PennockJL, GrencisRK (2006) The mast cell and gut nematodes: damage and defence. Chem Immunol Allergy 90: 128–140.

59. GalliSJ, MaurerM, LantzCS (1999) Mast cells as sentinels of innate immunity. Curr Opin Immunol 11: 53–59.

60. EchtenacherB, MännelDN, HültnerL (1996) Critical protective role of mast cells in a model of acute septic peritonitis. Nature 381: 75–77.

61. MalaviyaR, IkedaT, RossE, AbrahamSN (1996) Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-α. Nature 381: 77–80.

62. StassenM, HültnerL, SchmittE (2002) Classical and alternative pathways of mast cell activation. Crit Rev Immunol 22: 115–140.

63. HeibV, BeckerM, TaubeC, StassenM (2008) Advances in the understanding of mast cell function. Br J Haematol 142: 683–694.

64. St JohnAL, RathoreAP, YapH, NgML, MetcalfeDD, et al. (2011) Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance. Proc Natl Acad Sci USA 108: 9190–9195.

65. WangZ, LaiY, BernardJJ, MacleodDT, CogenAL, et al. (2012) Skin mast cells protect mice against vaccinia virus by triggering mast cell receptor S1PR2 and releasing antimicrobial peptides. J Immunol 188: 345–357.

66. AokiR, KawamuraT, GoshimaF, OgawaY, NakaeS, et al. (2013) Mast cells play a key role in host defense against herpes simplex virus infection through TNF-α and IL-6 production. J Invest Dermatol 133: 2170–2179.

67. AssarssonE, KambayashiT, SandbergJK, HongS, TaniguchiM, et al. (2000) CD8+ T cells rapidly acquire NK1.1 and NK cell-associated molecules upon stimulation in vitro and in vivo. J Immunol 165: 3673–3679.

68. KambayashiT, AssarssonE, MichaëlssonJ, BerglundP, DiehlAD, et al. (2000) Emergence of CD8+ T cells expressing NK cell receptors in influenza A virus-infected mice. J Immunol 165: 4964–4969.

69. Redwood AJ, Shellam GR, Smith LM (2013) Molecular evolution of murine cytomegalovirus genomes. In: Reddehase MJ, editor. Cytomegaloviruses: from molecular pathogenesis to intervention. Caister Academic Press, Norfolk, UK. Vol. I. pp 23–37

70. GalliSJ, KalesnikoffJ, GrimbaldestonMA, PiliponskyAM, WilliamsCM, et al. (2005) Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol 23: 749–786.

71. WagnerM, JonjicS, KoszinowskiUH, MesserleM (1999) Systematic excision of vector sequences from the BAC-cloned herpesvirus genome during virus reconstitution. J Virol 73: 7056–7060.

72. Podlech J, Holtappels R, Grzimek NK, Reddehase MJ (2002) Animal models: murine cytomegalovirus. In: Kaufmann SHE, Kabelitz D, editors. Methods in Microbiology: Immunology of Infection. 2nd ed. Academic Press, London. Pp 493–525.

73. CobboldSP, JayasuriyaA, NashA, ProsperoTD, WaldmannH (1984) Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature 312: 548–551.

74. JonjicS, PavicI, LucinP, RukavinaD, KoszinowskiUH (1990) Efficacious control of cytomegalovirus infection after long-term depletion of CD8+ T lymphocytes. J Virol 64: 5457–5464.

75. StassenM, ValevaA, WalevI, SchmittE (2006) Activation of mast cells by streptolysin O and lipopolysaccharide. Methods Mol Biol 315: 393–403.

76. ReuterS, HeinzA, SierenM, WiewrodtR, GelfandEW, et al. (2008) Mast cell-derived tumour necrosis factor is essential for allergic airway disease. Eur Respir J 31: 773–782.

77. ReuterS, DehzadN, MartinH, HeinzA, CastorT, et al. (2010) Mast cells induce migration of dendritic cells in a murine model of acute allergic airway disease. Int Arch Allergy Immunol 151: 214–222.

78. MaxeinerJH, KarwotR, HausdingM, SauerKA, ScholtesP, et al. (2007) A method to enable the investigation of murine bronchial immune cells, their cytokines and mediators. Nat Protoc 2: 105–112.

79. Pahl-SeibertMF, JuelchM, PodlechJ, ThomasD, DeegenP, et al. (2005) Highly protective in vivo function of cytomegalovirus IE1 epitope-specific memory CD8 T cells purified by T-cell receptor-based cell sorting. J Virol 79: 5400–5413.

80. BöhmV, SimonCO, PodlechJ, SeckertCK, GendigD, et al. (2008) The immune evasion paradox: immunoevasins of murine cytomegalovirus enhance priming of CD8 T cells by preventing negative feedback regulation. J Virol 82: 11637–11650.

81. Lemmermann NA, Podlech J, Seckert CK, Kropp KA, Grzimek NK, et al. (2010) CD8 T-cell immunotherapy of cytomegalovirus disease in the murine model. In: Kabelitz D, Kaufmann SHE, editors. Methods in Microbiology: Immunology of Infection. 3rd ed. Academic Press, London. pp 369–420.