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Late Engagement of CD86 after Influenza Virus Clearance Promotes Recovery in a FoxP3 Regulatory T Cell Dependent Manner


Influenza A virus (IAV) infection can cause severe inflammation and injury in the respiratory tract, which must be resolved and repaired for the host to fully recover after virus clearance. Evidence is emerging that host immune responses may regulate tissue repair and resolution of inflammation after IAV infection. Early in IAV infection, the co-stimulatory molecules CD80 and CD86 promote inflammation through triggering IAV-specific T cell responses, but no role for CD80/86 in recovery after virus clearance has been previously established. By in vivo antibody-mediated blockade of CD80 or CD86 after virus clearance, we found that engagement of CD86 (but not CD80) was required for optimal recovery after influenza infection. Furthermore, we determined that CD86 was essential for maintaining the FoxP3+regulatory T cell (Treg) population in the respiratory tract, and CD86-dependent Tregs promoted recovery by suppressing pulmonary inflammation and supporting regain of weight after virus clearance. In addition, we demonstrated that Tregs suppress neutrophils late after infection, preventing neutrophils from driving excess inflammatory cytokine release into the airways. Taken together, we propose a novel role for CD86 engagement late after IAV infection to promote resolution of inflammation and host recovery through a Treg-dependent mechanism.


Vyšlo v časopise: Late Engagement of CD86 after Influenza Virus Clearance Promotes Recovery in a FoxP3 Regulatory T Cell Dependent Manner. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004315
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004315

Souhrn

Influenza A virus (IAV) infection can cause severe inflammation and injury in the respiratory tract, which must be resolved and repaired for the host to fully recover after virus clearance. Evidence is emerging that host immune responses may regulate tissue repair and resolution of inflammation after IAV infection. Early in IAV infection, the co-stimulatory molecules CD80 and CD86 promote inflammation through triggering IAV-specific T cell responses, but no role for CD80/86 in recovery after virus clearance has been previously established. By in vivo antibody-mediated blockade of CD80 or CD86 after virus clearance, we found that engagement of CD86 (but not CD80) was required for optimal recovery after influenza infection. Furthermore, we determined that CD86 was essential for maintaining the FoxP3+regulatory T cell (Treg) population in the respiratory tract, and CD86-dependent Tregs promoted recovery by suppressing pulmonary inflammation and supporting regain of weight after virus clearance. In addition, we demonstrated that Tregs suppress neutrophils late after infection, preventing neutrophils from driving excess inflammatory cytokine release into the airways. Taken together, we propose a novel role for CD86 engagement late after IAV infection to promote resolution of inflammation and host recovery through a Treg-dependent mechanism.


Zdroje

1. DamjanovicD, SmallC-L, JeyananthanM, McCormickS, XingZ (2012) Immunopathology in influenza virus infection: Uncoupling the friend from foe. Clinical Immunology 144: 57–69.

2. ShortKR, KroezeEJBV, FouchierRAM, KuikenT (2014) Pathogenesis of influenza-induced acute respiratory distress syndrome. The Lancet Infectious Diseases 14: 57–69.

3. BracialeTJ, SunJ, KimTS (2012) Regulating the adaptive immune response to respiratory virus infection. Nat Rev Immunol 12: 295–305.

4. WeberB, SchusterS, ZyssetD, RihsS, DickgreberN, et al. (2014) TREM-1 Deficiency Can Attenuate Disease Severity without Affecting Pathogen Clearance. PLoS Pathog 10: e1003900.

5. ShireyKA, LaiW, ScottAJ, LipskyM, MistryP, et al. (2013) The TLR4 antagonist Eritoran protects mice from lethal influenza infection. Nature 497: 498–502.

6. AldridgeJR, MoseleyCE, BoltzDA, NegovetichNJ, ReynoldsC, et al. (2009) TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proceedings of the National Academy of Sciences 106: 5306–5311.

7. GorskiSA, HuffordMM, BracialeTJ (2012) Recent insights into pulmonary repair following virus-induced inflammation of the respiratory tract. Current Opinion in Virology 2: 233–241.

8. MonticelliLA, SonnenbergGF, AbtMC, AlenghatT, ZieglerCGK, et al. (2011) Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol 12: 1045–1054.

9. KumarP, ThakarMS, OuyangW, MalarkannanS (2013) IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection. Mucosal Immunol 6: 69–82.

10. LevyBD, SerhanCN (2013) Resolution of Acute Inflammation in the Lung. Annual Review of Physiology 76: 467–92.

11. D'AlessioFR, TsushimaK, AggarwalNR, WestEE, et al. (2009) CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury. The Journal of Clinical Investigation 119: 2898–2913.

12. SlavikJM, HutchcroftJE, BiererBE (1999) CD28/CTLA-4 and CD80/CD86 Families: Signaling and Function. Immunologic Research 19: 1–24.

13. Bour-JordanH, BluestoneJA (2009) Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells. Immunological Reviews 229: 41–66.

14. LiuY, WengerRH, ZhaoM, NielsenPJ (1997) Distinct costimulatory molecules are required for the induction of effector and memory cytotoxic T lymphocytes. J Exp Med 185: 251–262.

15. Dolfi D, Katsikis P (2007) CD28 and Cd27 Costimulation of Cd8+ T Cells: A Story of Survival. In: Katsikis P, Schoenberger S, Pulendran B, editors. Crossroads between Innate and Adaptive Immunity: Springer US. pp. 149–170.

16. SeahSGK, CarringtonEM, NgWC, BelzGT, BradyJL, et al. (2012) Unlike CD4+ T-cell help, CD28 costimulation is necessary for effective primary CD8+ T-cell influenza-specific immunity. European Journal of Immunology 42: 1744–1754.

17. HuffordMM, KimTS, SunJ, BracialeTJ (2011) Antiviral CD8+ T cell effector activities in situ are regulated by target cell type. The Journal of Experimental Medicine 208: 167–180.

18. DolfiDV, DuttaguptaPA, BoesteanuAC, MuellerYM, OliaiCH, et al. (2011) Dendritic cells and CD28 costimulation are required to sustain virus-specific CD8+ T cell responses during the effector phase in vivo. J Immunol 186: 4599–4608.

19. LenschowDJ, HoSC, SattarH, RheeL, GrayG, et al. (1995) Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse. The Journal of Experimental Medicine 181: 1145–1155.

20. PerezN, Karumuthil-MelethilS, LiR, PrabhakarBS, HoltermanMJ, et al. (2008) Preferential Costimulation by CD80 Results in IL-10-Dependent TGF-β1+-Adaptive Regulatory T Cell Generation. The Journal of Immunology 180: 6566–6576.

21. JosefowiczSZ, LuL-F, RudenskyAY (2012) Regulatory T Cells: Mechanisms of Differentiation and Function. Annual Review of Immunology 30: 531–64.

22. ChaudhryA, RudenskyAY (2013) Control of inflammation by integration of environmental cues by regulatory T cells. The Journal of Clinical Investigation 123: 939–944.

23. HaeryfarSMM, DiPaoloRJ, TscharkeDC, BenninkJR, YewdellJW (2005) Regulatory T Cells Suppress CD8+ T Cell Responses Induced by Direct Priming and Cross-Priming and Moderate Immunodominance Disparities. The Journal of Immunology 174: 3344–3351.

24. BettsRJ, HoAWS, KemenyDM (2011) Partial Depletion of Natural CD4+CD25+ Regulatory T Cells with Anti-CD25 Antibody Does Not Alter the Course of Acute Influenza A Virus Infection. PLoS ONE 6: e27849.

25. BrincksEL, RobertsAD, CookenhamT, SellS, KohlmeierJE, et al. (2013) Antigen-Specific Memory Regulatory CD4+Foxp3+ T Cells Control Memory Responses to Influenza Virus Infection. The Journal of Immunology 190: 3438–3446.

26. WangL, ZhaoL, LvJ, YinQ, LiangX, et al. (2012) BLT1-Dependent Alveolar Recruitment of CD4+CD25+ Foxp3+ Regulatory T Cells is Important for Resolution of Acute Lung Injury. American Journal of Respiratory and Critical Care Medicine 186 (10) 989–98.

27. EhrentrautH, ClambeyET, McNameeEN, BrodskyKS, EhrentrautSF, et al. (2013) CD73+ regulatory T cells contribute to adenosine-mediated resolution of acute lung injury. The FASEB Journal 27: 2207–2219.

28. LumsdenJM, RobertsJM, HarrisNL, PeachRJ, RoncheseF (2000) Differential Requirement for CD80 and CD80/CD86-Dependent Costimulation in the Lung Immune Response to an Influenza Virus Infection. The Journal of Immunology 164: 79–85.

29. ZengM, GuinetE, Nouri-ShiraziM (2009) B7-1 and B7-2 differentially control peripheral homeostasis of CD4+CD25+Foxp3+ regulatory T cells. Transplant Immunology 20: 171–179.

30. GreenwaldRJ, FreemanGJ, SharpeAH (2005) THE B7 FAMILY REVISITED. Annual Review of Immunology 23: 515–548.

31. EylesJL, RobertsAW, MetcalfD, WicksIP (2006) Granulocyte colony-stimulating factor and neutrophils[mdash]forgotten mediators of inflammatory disease. Nat Clin Pract Rheum 2: 500–510.

32. AntunesIs, KassiotisG (2010) Suppression of Innate Immune Pathology by Regulatory T Cells during Influenza A Virus Infection of Immunodeficient Mice. Journal of Virology 84: 12564–12575.

33. BettsRJ, PrabhuN, HoAWS, LewFC, HutchinsonPE, et al. (2012) Influenza A Virus Infection Results in a Robust, Antigen-Responsive and Widely Disseminated Foxp3+ Regulatory T Cell Response. Journal of Virology

34. Lahl K, Sparwasser T (2011) In Vivo Depletion of FoxP3+ Tregs Using the DEREG Mouse Model. In: Kassiotis G, Liston A, editors. Regulatory T Cells: Humana Press. pp. 157–172.

35. ChenG-Y, ChenC, WangL, ChangX, ZhengP, et al. (2008) Cutting Edge: Broad Expression of the FoxP3 Locus in Epithelial Cells: A Caution against Early Interpretation of Fatal Inflammatory Diseases following In Vivo Depletion of FoxP3-Expressing Cells. The Journal of Immunology 180: 5163–5166.

36. BertramEM, LauP, WattsTH (2002) Temporal Segregation of 4-1BB Versus CD28-Mediated Costimulation: 4-1BB Ligand Influences T Cell Numbers Late in the Primary Response and Regulates the Size of the T Cell Memory Response Following Influenza Infection. The Journal of Immunology 168: 3777–3785.

37. YadavD, JudkowskiV, Flodstrom-TullbergM, SterlingL, RedmondWL, et al. (2004) B7-2 (CD86) Controls the Priming of Autoreactive CD4 T Cell Response against Pancreatic Islets. The Journal of Immunology 173: 3631–3639.

38. YamazakiS, IyodaT, TarbellK, OlsonK, VelinzonK, et al. (2003) Direct Expansion of Functional CD25+ CD4+ Regulatory T Cells by Antigen-processing Dendritic Cells. The Journal of Experimental Medicine 198: 235–247.

39. PietropaoliA, GeorasSN (2009) Resolving lung injury: a new role for Tregs in controlling the innate immune response. The Journal of Clinical Investigation 119: 2891–2894.

40. SunJ, BracialeTJ (2013) Role of T cell immunity in recovery from influenza virus infection. Current Opinion in Virology 3: 425–429.

41. SalomonB, LenschowDJ, RheeL, AshourianN, SinghB, et al. (2000) B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12: 431–440.

42. ScheffoldA, HühnJ, HöferT (2005) Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL-)two to tango. European Journal of Immunology 35: 1336–1341.

43. ZouT, SatakeA, Corbo-RodgersE, SchmidtAM, FarrarMA, et al. (2012) Cutting Edge: IL-2 Signals Determine the Degree of TCR Signaling Necessary To Support Regulatory T Cell Proliferation In Vivo. The Journal of Immunology 189: 28–32.

44. OrabonaC, GrohmannU, BelladonnaML, FallarinoF, VaccaC, et al. (2004) CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86. Nat Immunol 5: 1134–1142.

45. TaylorPA, LeesCJ, FournierS, AllisonJP, SharpeAH, et al. (2004) B7 Expression on T Cells Down-Regulates Immune Responses through CTLA-4 Ligation via R-T Interactions. The Journal of Immunology 172: 34–39.

46. HuffordMM, RichardsonG, ZhouH, ManicassamyB, García-SastreA, et al. (2012) Influenza-Infected Neutrophils within the Infected Lungs Act as Antigen Presenting Cells for Anti-Viral CD8+ T Cells. PLoS ONE 7: e46581.

47. TateMD, DengY-M, JonesJE, AndersonGP, BrooksAG, et al. (2009) Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection. The Journal of Immunology 183: 7441–7450.

48. DamjanovicD, SmallC-L, JeyananthanM, McCormickS, XingZ (2012) Immunopathology in influenza virus infection: Uncoupling the friend from foe. Clinical Immunology 144: 57–69.

49. BrandesM, KlauschenF, KuchenS, Germain RonaldN (2013) A Systems Analysis Identifies a Feedforward Inflammatory Circuit Leading to Lethal Influenza Infection. Cell 154: 197–212.

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

51. BorregaardN (2014) What Doesn't Kill You Makes You Stronger: The Anti-inflammatory Effect of Neutrophil Respiratory Burst. Immunity 40: 1–2.

52. DienzO, RudJG, EatonSM, LanthierPA, BurgE, et al. (2012) Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung. Mucosal Immunol 5: 258–266.

53. ShiraziR, PalsdottirV, CollanderJ, AnestenF, VogelH, et al. (2013) Glucagon-like peptide 1 receptor induced suppression of food intake, and body weight is mediated by central IL-1 and IL-6. Proceedings of the National Academy of Sciences 110: 16199–16204.

54. LawrenceCW, BracialeTJ (2004) Activation, Differentiation, and Migration of Naive Virus-Specific CD8+ T Cells during Pulmonary Influenza Virus Infection. The Journal of Immunology 173: 1209–1218.

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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