The Immune Adaptor ADAP Regulates Reciprocal TGF-β1-Integrin Crosstalk to Protect from Influenza Virus Infection

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Infection of avian influenza virus, especially the highly pathogenic strain H5N1, is a serious threat to public health worldwide, which causes severe fatal respiratory disease and excessive levels of inflammation. It has been reported that both transforming growth factor-beta 1 (TGF-β1) and the integrin CD103 induced by TGF-β1 play protective roles in influenza virus infections. We aimed to find which protein regulates the TGF-β1-integrin cross-talk to protect against H5N1 virus infection. This study provides the first evidence that the intracellular signaling protein ADAP (adhesion and degranulation-promoting adapter protein) up-regulates TGF-β1 production and TGF-β1 induced CD103 expression in CD8+ T cells via the TβRI-TRAF6-TAK1-SMAD3 pathway. Importantly, in response to H5N1 and H1N1 virus infection, ADAP deficiency decreases TGF-β1 production and CD103 expression in lung infiltrating CD8+ T cells with the enhanced mortality in mice. Since various SNPs or mutations in key molecules of TGF-β1 pathway, including polymorphisms located in ADAP/FYB gene, are associated with inflammatory diseases, future work should investigate whether these SNPs or mutations enhance disease susceptibility or clinical manifestations in response to acute influenza virus infection.

Vyšlo v časopise: The Immune Adaptor ADAP Regulates Reciprocal TGF-β1-Integrin Crosstalk to Protect from Influenza Virus Infection. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004824
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004824

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1. Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, et al. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet. 2004;363(9409):617–9. 14987888

2. de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nature medicine. 2006;12(10):1203–7. 16964257

3. Tumpey TM, Lu X, Morken T, Zaki SR, Katz JM. Depletion of lymphocytes and diminished cytokine production in mice infected with a highly virulent influenza A (H5N1) virus isolated from humans. Journal of virology. 2000;74(13):6105–16. 10846094

4. Szretter KJ, Gangappa S, Lu X, Smith C, Shieh WJ, Zaki SR, et al. Role of host cytokine responses in the pathogenesis of avian H5N1 influenza viruses in mice. Journal of virology. 2007;81(6):2736–44. 17182684

5. Cilloniz C, Pantin-Jackwood MJ, Ni C, Goodman AG, Peng X, Proll SC, et al. Lethal dissemination of H5N1 influenza virus is associated with dysregulation of inflammation and lipoxin signaling in a mouse model of infection. Journal of virology. 2010;84(15):7613–24. doi: 10.1128/JVI.00553-10 20504916

6. Salomon R, Hoffmann E, Webster RG. Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. Proc Natl Acad Sci U S A. 2007;104(30):12479–81. 17640882

7. Massague J. TGF-beta signal transduction. Annual Review of Biochemistry. 1998;67:753–91. 9759503

8. Li MO, Wan YY, Sanjabi S, Robertson A- KL, Flavell RA. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol. 2006;24:99–146. 16551245

9. Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. Journal of cell science. 2003;116(Pt 2):217–24.

10. Carlson CM, Turpin EA, Moser LA, O'Brien KB, Cline TD, Jones JC, et al. Transforming growth factor-beta: activation by neuraminidase and role in highly pathogenic H5N1 influenza pathogenesis. PLoS pathogens. 2010;6(10):e1001136. doi: 10.1371/journal.ppat.1001136 20949074

11. Schultz-Cherry S, Hinshaw VS. Influenza virus neuraminidase activates latent transforming growth factor beta. Journal of virology. 1996;70(12):8624–9. 8970987

12. Kang SG, Park J, Cho JY, Ulrich B, Kim CH. Complementary roles of retinoic acid and TGF-[beta]1 in coordinated expression of mucosal integrins by T cells. Mucosal immunology. 2011;4(1):66–82. doi: 10.1038/mi.2010.42 20664575

13. Piet B, de Bree GJ, Smids-Dierdorp BS, van der Loos CM, Remmerswaal EB, von der Thusen JH, et al. CD8(+) T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung. The Journal of clinical investigation. 2011;121(6):2254–63. doi: 10.1172/JCI44675 21537083

14. Ray SJ, Franki SN, Pierce RH, Dimitrova S, Koteliansky V, Sprague AG, et al. The collagen binding alpha1beta1 integrin VLA-1 regulates CD8 T cell-mediated immune protection against heterologous influenza infection. Immunity. 2004;20(2):167–79. 14975239

15. Wang H, Wei B, Bismuth G, Rudd CE. SLP-76-ADAP adaptor module regulates LFA-1 mediated costimulation and T cell motility. Proceedings of the National Academy of Sciences. 2009;106(30):12436–41. doi: 10.1073/pnas.0900510106 19617540

16. Griffiths EK, Krawczyk C, Kong YY, Raab M, Hyduk SJ, Bouchard D, et al. Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap. Science. 2001;293(5538):2260–3. 11567140

17. Peterson EJ, Woods ML, Dmowski SA, Derimanov G, Jordan MS, Wu JN, et al. Coupling of the TCR to integrin activation by Slap-130/Fyb. Science. 2001;293(5538):2263–5. 11567141

18. Medeiros RB, Burbach BJ, Mueller KL, Srivastava R, Moon JJ, Highfill S, et al. Regulation of NF-kappaB activation in T cells via association of the adapter proteins ADAP and CARMA1. Science. 2007;316(5825):754–8. 17478723

19. Suzuki J, Yamasaki S, Wu J, Koretzky GA, Saito T. The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation. Blood. 2007;109(1):168–75. 16973965

20. Liu G, Ding W, Neiman J, Mulder KM. Requirement of Smad3 and CREB-1 in mediating transforming growth factor-beta (TGF beta) induction of TGF beta 3 secretion. The Journal of biological chemistry. 2006;281(40):29479–90. 16891311

21. Tang B, Bottinger EP, Jakowlew SB, Bagnall KM, Mariano J, Anver MR, et al. Transforming growth factor-beta1 is a new form of tumor suppressor with true haploid insufficiency. Nature medicine. 1998;4(7):802–7. 9662371

22. Dennler S, Itoh S, Vivien D, ten Dijke P, Huet S, Gauthier JM. Direct binding of Smad3 and Smad4 to critical TGF beta-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene. The EMBO journal. 1998;17(11):3091–100. 9606191

23. Jonk LJ, Itoh S, Heldin CH, ten Dijke P, Kruijer W. Identification and functional characterization of a Smad binding element (SBE) in the JunB promoter that acts as a transforming growth factor-beta, activin, and bone morphogenetic protein-inducible enhancer. The Journal of biological chemistry. 1998;273(33):21145–52. 9694870

24. Conery AR, Cao Y, Thompson EA, Townsend CM Jr., Ko TC, Luo K. Akt interacts directly with Smad3 to regulate the sensitivity to TGF-beta induced apoptosis. Nature cell biology. 2004;6(4):366–72. 15104092

25. Remy I, Montmarquette A, Michnick SW. PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3. Nature cell biology. 2004;6(4):358–65. 15048128

26. Runyan CE, Schnaper HW, Poncelet AC. The phosphatidylinositol 3-kinase/Akt pathway enhances Smad3-stimulated mesangial cell collagen I expression in response to transforming growth factor-beta1. The Journal of biological chemistry. 2004;279(4):2632–9. 14610066

27. Zhang YE. Non-Smad pathways in TGF-beta signaling. Cell research. 2009;19(1):128–39. doi: 10.1038/cr.2008.328 19114990

28. Kretzschmar M, Doody J, Timokhina I, Massague J. A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras. Genes & development. 1999;13(7):804–16.

29. Moustakas A, Heldin CH. Non-Smad TGF-beta signals. Journal of cell science. 2005;118(Pt 16):3573–84. 16105881

30. Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, et al. The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nature cell biology. 2008;10(10):1199–207. doi: 10.1038/ncb1780 18758450

31. Jiao P, Tian G, Li Y, Deng G, Jiang Y, Liu C, et al. A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. Journal of virology. 2008;82(3):1146–54. 18032512

32. Zou L, Mendez F, Martin-Orozco N, Peterson EJ. Defective positive selection results in T cell lymphopenia and increased autoimmune diabetes in ADAP-deficient BDC2.5-C57BL/6 mice. European journal of immunology. 2008;38(4):986–94. doi: 10.1002/eji.200737881 18383041

33. Srivastava R, Burbach BJ, Mitchell JS, Pagan AJ, Shimizu Y. ADAP regulates cell cycle progression of T cells via control of cyclin E and Cdk2 expression through two distinct CARMA1-dependent signaling pathways. Molecular and cellular biology. 2012;32(10):1908–17. doi: 10.1128/MCB.06541-11 22411628

34. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70. 10647931

35. Wipff PJ, Rifkin DB, Meister JJ, Hinz B. Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. The Journal of cell biology. 2007;179(6):1311–23. 18086923

36. Li Q, Zhou L, Zhou M, Chen Z, Li F, Wu H, et al. Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China. New England Journal of Medicine. 2014;370(6):520–32. doi: 10.1056/NEJMoa1304617 23614499

37. Chen Y, Liang W, Yang S, Wu N, Gao H, Sheng J, et al. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet. 2013;381(9881):1916–25. doi: 10.1016/S0140-6736(13)60903-4 23623390

38. Laidlaw BJ, Decman V, Ali MA, Abt MC, Wolf AI, Monticelli LA, et al. Cooperativity Between CD8+ T Cells, Non-Neutralizing Antibodies, and Alveolar Macrophages Is Important for Heterosubtypic Influenza Virus Immunity. PLoS pathogens. 2013;9(3):e1003207. doi: 10.1371/journal.ppat.1003207 23516357

39. Wu H, Kumar A, Miao H, Holden-Wiltse J, Mosmann TR, Livingstone AM, et al. Modeling of influenza-specific CD8+ T cells during the primary response indicates that the spleen is a major source of effectors. Journal of immunology. 2011;187(9):4474–82. doi: 10.4049/jimmunol.1101443 21948988

40. Mokrani M, Klibi J, Bluteau D, Bismuth G, Mami-Chouaib F. Smad and NFAT Pathways Cooperate To Induce CD103 Expression in Human CD8 T Lymphocytes. J Immunol. 2014;192(5):2471–9. doi: 10.4049/jimmunol.1302192 24477908

41. Uss E, Rowshani AT, Hooibrink B, Lardy NM, van Lier RA, ten Berge IJ. CD103 is a marker for alloantigen-induced regulatory CD8+ T cells. Journal of immunology. 2006;177(5):2775–83. 16920912

42. Lee JC, Espeli M, Anderson CA, Linterman MA, Pocock JM, Williams NJ, et al. Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway. Cell. 2013;155(1):57–69. doi: 10.1016/j.cell.2013.08.034 24035192

43. Chen T, Triplett J, Dehner B, Hurst B, Colligan B, Pemberton J, et al. Transforming Growth Factor-β Receptor Type I Gene Is Frequently Mutated in Ovarian Carcinomas. Cancer research. 2001;61(12):4679–82. 11406536

44. Antony ML, Nair R, Sebastian P, Karunagaran D. Changes in expression, and/or mutations in TGF-beta receptors (TGF-beta RI and TGF-beta RII) and Smad 4 in human ovarian tumors. Journal of cancer research and clinical oncology. 2010;136(3):351–61. doi: 10.1007/s00432-009-0703-4 19916025

45. Addobbati C, Brandao LA, Guimaraes RL, Pancotto JA, Donadi EA, Crovella S, et al. FYB gene polymorphisms are associated with susceptibility for systemic lupus erythemathosus (SLE). Human immunology. 2013;74(8):1009–14. doi: 10.1016/j.humimm.2013.04.026 23628395

46. Crowe CR, Chen K, Pociask DA, Alcorn JF, Krivich C, Enelow RI, et al. Critical Role of IL-17RA in Immunopathology of Influenza Infection. Journal of immunology. 2009;183(8):5301–10. doi: 10.4049/jimmunol.0900995 19783685

47. Wang X, Chan CCS, Yang M, Deng J, Poon VKM, Leung VHC, et al. A critical role of IL-17 in modulating the B-cell response during H5N1 influenza virus infection. Cellular & molecular immunology. 2011;8(6):462–8.

48. Lawrence CW, Ream RM, Braciale TJ. Frequency, specificity, and sites of expansion of CD8(+) T cells during primary pulmonary influenza virus infection. Journal of immunology. 2005;174(9):5332–40. 15843530