Expression of Suppressor of Cytokine Signaling 1 (SOCS1) Impairs Viral Clearance and Exacerbates Lung Injury during Influenza Infection

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Cytokines are critical in regulating the balance between protective immunity and detrimental inflammation during influenza infection. Suppressor of cytokine signaling (SOCS) proteins are inducible feedback inhibitors of cytokine signaling. Using gene-deficient and infectious animal models, we determined how SOCS1 regulates immune defense against influenza infection. We show that the intracellular protein SOCS1 not only inhibits adaptive antiviral immune responses but also exacerbates inflammatory lung damage. These detrimental effects of SOCS1 are conveyed through discrete cell populations. Specifically, while SOCS1 expression in adaptive immune cells is sufficient to inhibit antiviral immunity, SOCS1 in innate/stromal cells is responsible for aggravated lung injury. To our knowledge, there is no report showing the regulatory role of SOCS1 during the course of influenza infection, and importantly, no evidence directly linking SOCS1 with excessive inflammation in other infectious disease models. The distinct and non-competing detrimental roles of SOCS1, as revealed in this study, make it an appealing target in the design of effective immunotherapies for combating influenza infection.

Vyšlo v časopise: Expression of Suppressor of Cytokine Signaling 1 (SOCS1) Impairs Viral Clearance and Exacerbates Lung Injury during Influenza Infection. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004560
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004560

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1. PeirisJS, HuiKP, YenHL (2010) Host response to influenza virus: protection versus immunopathology. Curr Opin Immunol 22 : 475–481.

2. AlexanderWS, HiltonDJ (2004) The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu Rev Immunol 22 : 503–529.

3. DalpkeA, HeegK, BartzH, BaetzA (2008) Regulation of innate immunity by suppressor of cytokine signaling (SOCS) proteins. Immunobiology 213 : 225–235.

4. YoshimuraA, NakaT, KuboM (2007) SOCS proteins, cytokine signalling and immune regulation. Nat Rev Immunol 7 : 454–465.

5. PauliEK, SchmolkeM, WolffT, ViemannD, RothJ, et al. (2008) Influenza A virus inhibits type I IFN signaling via NF-kappaB-dependent induction of SOCS-3 expression. PLoS Pathog 4: e1000196.

6. PothlichetJ, ChignardM, Si-TaharM (2008) Cutting edge: innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway. J Immunol 180 : 2034–2038.

7. WeiH, WangS, ChenQ, ChenY, ChiX, et al. (2014) Suppression of interferon lambda signaling by SOCS-1 results in their excessive production during influenza virus infection. PLoS Pathog 10: e1003845.

8. ChongMM, MetcalfD, JamiesonE, AlexanderWS, KayTW (2005) Suppressor of cytokine signaling-1 in T cells and macrophages is critical for preventing lethal inflammation. Blood 106 : 1668–1675.

9. DimitriouID, ClemenzaL, ScotterAJ, ChenG, GuerraFM, et al. (2008) Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins. Immunol Rev 224 : 265–283.

10. DickensheetsH, VazquezN, SheikhF, GingrasS, MurrayPJ, et al. (2007) Suppressor of cytokine signaling-1 is an IL-4-inducible gene in macrophages and feedback inhibits IL-4 signaling. Genes Immun 8 : 21–27.

11. LeeC, KolesnikTB, CaminschiI, ChakravortyA, CarterW, et al. (2009) Suppressor of cytokine signalling 1 (SOCS1) is a physiological regulator of the asthma response. Clin Exp Allergy 39 : 897–907.

12. EgwuaguCE, YuCR, ZhangM, MahdiRM, KimSJ, et al. (2002) Suppressors of cytokine signaling proteins are differentially expressed in Th1 and Th2 cells: implications for Th cell lineage commitment and maintenance. J Immunol 168 : 3181–3187.

13. SunK, TorresL, MetzgerDW (2010) A detrimental effect of interleukin-10 on protective pulmonary humoral immunity during primary influenza A virus infection. J Virol 84 : 5007–5014.

14. StarrR, MetcalfD, ElefantyAG, BryshaM, WillsonTA, et al. (1998) Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1. Proc Natl Acad Sci U S A 95 : 14395–14399.

15. MarineJC, TophamDJ, McKayC, WangD, ParganasE, et al. (1999) SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell 98 : 609–616.

16. BrownDM, DilzerAM, MeentsDL, SwainSL (2006) CD4 T cell-mediated protection from lethal influenza: perforin and antibody-mediated mechanisms give a one-two punch. J Immunol 177 : 2888–2898.

17. La GrutaNL, KedzierskaK, StambasJ, DohertyPC (2007) A question of self-preservation: immunopathology in influenza virus infection. Immunol Cell Biol 85 : 85–92.

18. FennerJE, StarrR, CornishAL, ZhangJG, MetcalfD, et al. (2006) Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity. Nat Immunol 7 : 33–39.

19. NakashimaT, YokoyamaA, OnariY, ShodaH, HarutaY, et al. (2008) Suppressor of cytokine signaling 1 inhibits pulmonary inflammation and fibrosis. J Allergy Clin Immunol 121 : 1269–1276.

20. UnkelB, HoegnerK, ClausenBE, Lewe-SchlosserP, BodnerJ, et al. (2012) Alveolar epithelial cells orchestrate DC function in murine viral pneumonia. J Clin Invest 122 : 3652–3664.

21. TurnerSJ, OlivasE, GutierrezA, DiazG, DohertyPC (2007) Disregulated influenza A virus-specific CD8+ T cell homeostasis in the absence of IFN-gamma signaling. J Immunol 178 : 7616–7622.

22. DawsonTC, BeckMA, KuzielWA, HendersonF, MaedaN (2000) Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus. Am J Pathol 156 : 1951–1959.

23. LinKL, SweeneyS, KangBD, RamsburgE, GunnMD (2011) CCR2-antagonist prophylaxis reduces pulmonary immune pathology and markedly improves survival during influenza infection. J Immunol 186 : 508–515.

24. SeoSU, KwonHJ, KoHJ, ByunYH, SeongBL, et al. (2011) Type I interferon signaling regulates Ly6C(hi) monocytes and neutrophils during acute viral pneumonia in mice. PLoS Pathog 7: e1001304.

25. WareingMD, SheaAL, InglisCA, DiasPB, SarawarSR (2007) CXCR2 is required for neutrophil recruitment to the lung during influenza virus infection, but is not essential for viral clearance. Viral Immunol 20 : 369–378.

26. AldridgeJRJr, MoseleyCE, BoltzDA, NegovetichNJ, ReynoldsC, et al. (2009) TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci U S A 106 : 5306–5311.

27. VlahosR, StambasJ, BozinovskiS, BroughtonBR, DrummondGR, et al. (2011) Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation. PLoS Pathog 7: e1001271.

28. SnelgroveRJ, EdwardsL, RaeAJ, HussellT (2006) An absence of reactive oxygen species improves the resolution of lung influenza infection. Eur J Immunol 36 : 1364–1373.

29. LeePY, WangJX, ParisiniE, DascherCC, NigrovicPA (2013) Ly6 family proteins in neutrophil biology. J Leukoc Biol 94 : 585–594.

30. GeissmannF, ManzMG, JungS, SiewekeMH, MeradM, et al. (2010) Development of monocytes, macrophages, and dendritic cells. Science 327 : 656–661.

31. MiaoH, HollenbaughJA, ZandMS, Holden-WiltseJ, MosmannTR, et al. (2010) Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus. J Virol 84 : 6687–6698.

32. BaumgarthN, HermanOC, JagerGC, BrownLE, HerzenbergLA, et al. (2000) B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J Exp Med 192 : 271–280.

33. BaumgarthN (2013) How specific is too specific? B-cell responses to viral infections reveal the importance of breadth over depth. Immunol Rev 255 : 82–94.

34. RamosI, CarneroE, Bernal-RubioD, SeibertCW, WesteraL, et al. (2013) Contribution of double-stranded RNA and CPSF30 binding domains of influenza virus NS1 to the inhibition of type I interferon production and activation of human dendritic cells. J Virol 87 : 2430–2440.

35. NakamuraS, DavisKM, WeiserJN (2011) Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice. J Clin Invest 121 : 3657–3665.

36. PalmerDC, RestifoNP (2009) Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and function. Trends Immunol 30 : 592–602.

37. SvetlikovaD, KabatP, OhradanovaA, PastorekJ, BetakovaT (2010) Influenza A virus replication is inhibited in IFN-lambda2 and IFN-lambda3 transfected or stimulated cells. Antiviral Res 88 : 329–333.

38. HikonoH, KohlmeierJE, ElyKH, ScottI, RobertsAD, et al. (2006) T-cell memory and recall responses to respiratory virus infections. Immunol Rev 211 : 119–132.

39. LinKL, SuzukiY, NakanoH, RamsburgE, GunnMD (2008) CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. J Immunol 180 : 2562–2572.

40. YasukawaH, YajimaT, DuplainH, IwatateM, KidoM, et al. (2003) The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury. J Clin Invest 111 : 469–478.

41. WileyJA, CerwenkaA, HarkemaJR, DuttonRW, HarmsenAG (2001) Production of interferon-gamma by influenza hemagglutinin-specific CD8 effector T cells influences the development of pulmonary immunopathology. Am J Pathol 158 : 119–130.

42. MoranTM, IsobeH, Fernandez-SesmaA, SchulmanJL (1996) Interleukin-4 causes delayed virus clearance in influenza virus-infected mice. J Virol 70 : 5230–5235.

43. SunJ, MadanR, KarpCL, BracialeTJ (2009) Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 15 : 277–284.

44. ChoH, KelsallBL (2014) The role of type I interferons in intestinal infection, homeostasis, and inflammation. Immunol Rev 260 : 145–167.

45. BullenDV, BaldwinTM, CurtisJM, AlexanderWS, HandmanE (2003) Persistence of lesions in suppressor of cytokine signaling-1-deficient mice infected with Leishmania major. J Immunol 170 : 4267–4272.

46. AlexanderWS, StarrR, FennerJE, ScottCL, HandmanE, et al. (1999) SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell 98 : 597–608.

47. HuprikarJ, RabinowitzS (1980) A simplified plaque assay for influenza viruses in Madin-Darby kidney (MDCK) cells. J Virol Methods 1 : 117–120.

48. DimayugaPC, CesenaFH, ChyuKY, YanoJ, AmornA, et al. (2009) Natural antibodies and complement modulate intimal thickening after arterial injury. Am J Physiol Regul Integr Comp Physiol 297: R1593–1600.

49. KambayashiT, AssarssonE, ChambersBJ, LjunggrenHG (2001) Expression of the DX5 antigen on CD8+ T cells is associated with activation and subsequent cell death or memory during influenza virus infection. Eur J Immunol 31 : 1523–1530.

50. MeissnerNN, LundFE, HanS, HarmsenA (2005) CD8 T cell-mediated lung damage in response to the extracellular pathogen pneumocystis is dependent on MHC class I expression by radiation-resistant lung cells. J Immunol 175 : 8271–8279.