STING-Dependent Type I IFN Production Inhibits Cell-Mediated Immunity to

English version České info

Infection with Listeria monocytogenes strains that enter the host cell cytosol leads to a robust cytotoxic T cell response resulting in long-lived cell-mediated immunity (CMI). Upon entry into the cytosol, L. monocytogenes secretes cyclic diadenosine monophosphate (c-di-AMP) which activates the innate immune sensor STING leading to the expression of IFN-β and co-regulated genes. In this study, we examined the role of STING in the development of protective CMI to L. monocytogenes. Mice deficient for STING or its downstream effector IRF3 restricted a secondary lethal challenge with L. monocytogenes and exhibited enhanced immunity that was MyD88-independent. Conversely, enhancing STING activation during immunization by co-administration of c-di-AMP or by infection with a L. monocytogenes mutant that secretes elevated levels of c-di-AMP resulted in decreased protective immunity that was largely dependent on the type I interferon receptor. These data suggest that L. monocytogenes activation of STING downregulates CMI by induction of type I interferon.

Vyšlo v časopise: STING-Dependent Type I IFN Production Inhibits Cell-Mediated Immunity to. PLoS Pathog 10(1): e32767. doi:10.1371/journal.ppat.1003861
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003861

Souhrn

Zdroje

1. HartyJT, TvinnereimAR, WhiteDW (2000) CD8+ T cell effector mechanisms in resistance to infection. Annual review of immunology 18: 275–308.

2. PamerEG (2004) Immune responses to Listeria monocytogenes. Nat Rev Immunol 4: 812–823.

3. SchentenD, MedzhitovR (2011) The control of adaptive immune responses by the innate immune system. Advances in immunology 109: 87–124.

4. WitteCE, ArcherKA, RaeCS, SauerJD, WoodwardJJ, et al. (2012) Innate immune pathways triggered by Listeria monocytogenes and their role in the induction of cell-mediated immunity. Advances in immunology 113: 135–156.

5. LeberJH, CrimminsGT, RaghavanS, Meyer-MorseNP, CoxJS, et al. (2008) Distinct TLR- and NLR-mediated transcriptional responses to an intracellular pathogen. PLoS Pathog 4: e6.

6. CossartP, Toledo-AranaA (2008) Listeria monocytogenes, a unique model in infection biology: an overview. Microbes and infection/Institut Pasteur 10: 1041–1050.

7. O'RiordanM, YiCH, GonzalesR, LeeKD, PortnoyDA (2002) Innate recognition of bacteria by a macrophage cytosolic surveillance pathway. Proc Natl Acad Sci U S A 99: 13861–13866.

8. BarberGN (2011) Innate immune DNA sensing pathways: STING, AIMII and the regulation of interferon production and inflammatory responses. Current opinion in immunology 23: 10–20.

9. BarkerJR, KoestlerBJ, CarpenterVK, BurdetteDL, WatersCM, et al. (2013) STING-dependent recognition of cyclic di-AMP mediates type I interferon responses during Chlamydia trachomatis infection. mBio 4: e00018–00013.

10. ZhangX, ShiH, WuJ, SunL, ChenC, et al. (2013) Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING. Molecular cell 51: 226–235.

11. BurdetteDL, MonroeKM, Sotelo-TrohaK, IwigJS, EckertB, et al. (2011) STING is a direct innate immune sensor of cyclic di-GMP. Nature 478: 515–518.

12. IshikawaH, MaZ, BarberGN (2009) STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461: 788–792.

13. McWhirterSM, BarbalatR, MonroeKM, FontanaMF, HyodoM, et al. (2009) A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP. J Exp Med 206: 1899–1911.

14. CrimminsGT, HerskovitsAA, RehderK, SivickKE, LauerP, et al. (2008) Listeria monocytogenes multidrug resistance transporters activate a cytosolic surveillance pathway of innate immunity. Proc Natl Acad Sci U S A 105: 10191–10196.

15. WoodwardJJ, IavaroneAT, PortnoyDA (2010) c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science 328: 1703–1705.

16. JinL, HillKK, FilakH, MoganJ, KnowlesH, et al. (2011) MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP. Journal of immunology 187: 2595–2601.

17. SauerJD, Sotelo-TrohaK, von MoltkeJ, MonroeKM, RaeCS, et al. (2011) The N-Ethyl-N-Nitrosourea-Induced Goldenticket Mouse Mutant Reveals an Essential Function of Sting in the In Vivo Interferon Response to Listeria monocytogenes and Cyclic Dinucleotides. Infect Immun 79: 688–694.

18. EbensenT, LibanovaR, SchulzeK, YevsaT, MorrM, et al. (2011) Bis-(3′,5′)-cyclic dimeric adenosine monophosphate: Strong Th1/Th2/Th17 promoting mucosal adjuvant. Vaccine 29: 5210–5220.

19. EbensenT, SchulzeK, RieseP, LinkC, MorrM, et al. (2007) The bacterial second messenger cyclic diGMP exhibits potent adjuvant properties. Vaccine 25: 1464–1469.

20. KaraolisDK, MeansTK, YangD, TakahashiM, YoshimuraT, et al. (2007) Bacterial c-di-GMP is an immunostimulatory molecule. J Immunol 178: 2171–2181.

21. BahjatKS, LiuW, LemmensEE, SchoenbergerSP, PortnoyDA, et al. (2006) Cytosolic entry controls CD8+-T-cell potency during bacterial infection. Infect Immun 74: 6387–6397.

22. BercheP, GaillardJL, SansonettiPJ (1987) Intracellular growth of Listeria monocytogenes as a prerequisite for in vivo induction of T cell-mediated immunity. J Immunol 138: 2266–2271.

23. von KoenigCH, FingerH, HofH (1982) Failure of killed Listeria monocytogenes vaccine to produce protective immunity. Nature 297: 233–234.

24. HartyJT, BevanMJ (1995) Specific immunity to Listeria monocytogenes in the absence of IFN gamma. Immunity 3: 109–117.

25. EdelsonBT, UnanueER (2002) MyD88-dependent but Toll-like receptor 2-independent innate immunity to Listeria: no role for either in macrophage listericidal activity. Journal of immunology 169: 3869–3875.

26. KursarM, MittruckerHW, KochM, KohlerA, HermaM, et al. (2004) Protective T cell response against intracellular pathogens in the absence of Toll-like receptor signaling via myeloid differentiation factor 88. International immunology 16: 415–421.

27. SekiE, TsutsuiH, TsujiNM, HayashiN, AdachiK, et al. (2002) Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice. Journal of immunology 169: 3863–3868.

28. WaySS, KollmannTR, HajjarAM, WilsonCB (2003) Cutting edge: protective cell-mediated immunity to Listeria monocytogenes in the absence of myeloid differentiation factor 88. J Immunol 171: 533–537.

29. ChenH, SunH, YouF, SunW, ZhouX, et al. (2011) Activation of STAT6 by STING is critical for antiviral innate immunity. Cell 147: 436–446.

30. IshikawaH, BarberGN (2008) STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455: 674–678.

31. CondottaSA, RicherMJ, BadovinacVP, HartyJT (2012) Probing CD8 T cell responses with Listeria monocytogenes infection. Advances in immunology 113: 51–80.

32. StockingerS, KastnerR, KernbauerE, PilzA, WestermayerS, et al. (2009) Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes. PLoS pathogens 5: e1000355.

33. KepplerSJ, RosenitsK, KoeglT, VucikujaS, AicheleP (2012) Signal 3 cytokines as modulators of primary immune responses during infections: the interplay of type I IFN and IL-12 in CD8 T cell responses. PLoS One 7: e40865.

34. ThompsonLJ, KolumamGA, ThomasS, Murali-KrishnaK (2006) Innate inflammatory signals induced by various pathogens differentially dictate the IFN-I dependence of CD8 T cells for clonal expansion and memory formation. J Immunol 177: 1746–1754.

35. CarreroJA, CalderonB, UnanueER (2004) Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection. J Exp Med 200: 535–540.

36. HuangL, LemosHP, LiL, LiM, ChandlerPR, et al. (2012) Engineering DNA nanoparticles as immunomodulatory reagents that activate regulatory T cells. Journal of immunology 188: 4913–4920.

37. HuangL, LiL, LemosH, ChandlerPR, PacholczykG, et al. (2013) Cutting Edge: DNA Sensing via the STING Adaptor in Myeloid Dendritic Cells Induces Potent Tolerogenic Responses. Journal of immunology 191: 3509–13.

38. AbdullahZ, SchleeM, RothS, MraheilMA, BarchetW, et al. (2012) RIG-I detects infection with live Listeria by sensing secreted bacterial nucleic acids. The EMBO journal 31: 4153–4164.

39. HagmannCA, HerznerAM, AbdullahZ, ZillingerT, JakobsC, et al. (2013) RIG-I Detects Triphosphorylated RNA of Listeria monocytogenes during Infection in Non-Immune Cells. PLoS One 8: e62872.

40. Brzoza-LewisKL, HothJJ, HiltboldEM (2012) Type I interferon signaling regulates the composition of inflammatory infiltrates upon infection with Listeria monocytogenes. Cellular immunology 273: 41–51.

41. MarshallHD, UrbanSL, WelshRM (2011) Virus-induced transient immune suppression and the inhibition of T cell proliferation by type I interferon. Journal of virology 85: 5929–5939.

42. NgoiSM, St RoseMC, MenoretAM, SmithDE, ToveyMG, et al. (2012) Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness. Proceedings of the National Academy of Sciences of the United States of America 109: 10486–10491.

43. MonroeKM, McWhirterSM, VanceRE (2010) Induction of type I interferons by bacteria. Cellular microbiology 12: 881–890.

44. AuerbuchV, BrockstedtDG, Meyer-MorseN, O'RiordanM, PortnoyDA (2004) Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J Exp Med 200: 527–533.

45. O'ConnellRM, SahaSK, VaidyaSA, BruhnKW, MirandaGA, et al. (2004) Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J Exp Med 200: 437–445.

46. SchwartzKT, CarletonJD, QuillinSJ, RollinsSD, PortnoyDA, et al. (2012) Hyperinduction of host beta interferon by a Listeria monocytogenes strain naturally overexpressing the multidrug efflux pump MdrT. Infection and immunity 80: 1537–1545.

47. WilsonEB, YamadaDH, ElsaesserH, HerskovitzJ, DengJ, et al. (2013) Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science 340: 202–207.

48. TeijaroJR, NgC, LeeAM, SullivanBM, SheehanKC, et al. (2013) Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science 340: 207–211.

49. ManzanilloPS, ShilohMU, PortnoyDA, CoxJS (2012) Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages. Cell host & microbe 11: 469–480.

50. TelescaC, AngelicoM, PiccoloP, NosottiL, MorroneA, et al. (2007) Interferon-alpha treatment of hepatitis D induces tuberculosis exacerbation in an immigrant. The Journal of infection 54: e223–226.

51. BerryMP, GrahamCM, McNabFW, XuZ, BlochSA, et al. (2010) An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466: 973–977.

52. DinerEJ, BurdetteDL, WilsonSC, MonroeKM, KellenbergerCA, et al. (2013) The Innate Immune DNA Sensor cGAS Produces a Noncanonical Cyclic Dinucleotide that Activates Human STING. Cell reports 3: 1355–1361.

53. PearceEL, ShenH (2007) Generation of CD8 T cell memory is regulated by IL-12. Journal of immunology 179: 2074–2081.

54. SauerJD, PereyreS, ArcherKA, BurkeTP, HansonB, et al. (2011) Listeria monocytogenes engineered to activate the Nlrc4 inflammasome are severely attenuated and are poor inducers of protective immunity. Proceedings of the National Academy of Sciences of the United States of America 108: 12419–12424.

55. BahjatKS, Meyer-MorseN, LemmensEE, ShugartJA, DubenskyTW, et al. (2009) Suppression of cell-mediated immunity following recognition of phagosome-confined bacteria. PLoS pathogens 5: e1000568.

56. BadovinacVP, PorterBB, HartyJT (2004) CD8+ T cell contraction is controlled by early inflammation. Nature immunology 5: 809–817.

57. BrockstedtDG, GiedlinMA, LeongML, BahjatKS, GaoY, et al. (2004) Listeria-based cancer vaccines that segregate immunogenicity from toxicity. Proc Natl Acad Sci U S A 101: 13832–13837.

58. WitteCE, WhiteleyAT, BurkeTP, SauerJD, PortnoyDA, et al. (2013) Cyclic di-AMP Is Critical for Listeria monocytogenes Growth, Cell Wall Homeostasis, and Establishment of Infection. mBio 4: e00282–13.

59. PortnoyDA, JacksPS, HinrichsDJ (1988) Role of hemolysin for the intracellular growth of Listeria monocytogenes. J Exp Med 167: 1459–1471.