Natural killer cells expanded in vivo or ex vivo with IL-15 overcomes the inherent susceptibility of CAST mice to lethal infection with orthopoxviruses

English version

Autoři: Patricia L. Earl ^aff001; Jeffrey L. Americo ^aff001; Bernard Moss ^aff001
Působiště autorů: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America ^aff001
Vyšlo v časopise: Natural killer cells expanded in vivo or ex vivo with IL-15 overcomes the inherent susceptibility of CAST mice to lethal infection with orthopoxviruses. PLoS Pathog 16(4): e32767. doi:10.1371/journal.ppat.1008505
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008505

Souhrn

The wild-derived inbred CAST/EiJ mouse, one of eight founder strains in the Collaborative Cross panel, is an exceptional model for studying monkeypox virus (MPXV), an emerging human pathogen, and other orthopoxviruses including vaccinia virus (VACV). Previous studies suggested that the extreme susceptibility of the CAST mouse to orthopoxviruses is due to an insufficient innate immune response. Here, we focused on the low number of natural killer (NK) cells in the naïve CAST mouse as a contributing factor to this condition. Administration of IL-15 to CAST mice transiently increased NK and CD8⁺ T cells that could express IFN-γ, indicating that the progenitor cells were capable of responding to cytokines. However, the number of NK cells rapidly declined indicating a defect in their homeostasis. Furthermore, IL-15-treated mice were protected from an otherwise lethal challenge with VACV or MPXV. IL-15 decreased virus spread and delayed death even when CD4⁺/CD8⁺ T cells were depleted with antibody, supporting an early protective role of the expanded NK cells. Purified splenic NK cells from CAST mice proliferated in vitro in response to IL-15 and could be activated with IL-12/IL-18 to secrete interferon-γ. Passive transfer of non-activated or activated CAST NK cells reduced VACV spread but only the latter completely prevented death at the virus dose used. Moreover, antibodies to interferon-γ abrogated the protection by activated NK cells. Thus, the inherent susceptibility of CAST mice to orthopoxviruses can be explained by a low level of NK cells and this vulnerability can be overcome either by expanding their NK cells in vivo with IL-15 or by passive transfer of purified NK cells that were expanded and activated in vitro.

Klíčová slova:

Cell staining – Inbred strains – Luminescence – Mouse models – NK cells – Photons – Spleen – T cells

Zdroje

1. Damon I. Poxviruses. In: Knipe DM, Howley PM, editors. Fields Virology. 2. Sixth ed. Philadelphia: Wolters Kluwer/ Lippincott Williams &Wilkins; 2013. p. 2160–84.

2. Kantele A, Chickering K, Vapalahti O, Rimoin AW. Emerging diseases-the monkeypox epidemic in the Democratic Republic of the Congo. Clinical Microbiology and Infection. 2016;22(8):658–9. doi: 10.1016/j.cmi.2016.07.004 WOS:000383824200003. 27404372

3. Yinka-Ogunleye A, Aruna O, Ogoina D, Aworabhi N, Eteng W, Badaru S, et al. Reemergence of Human Monkeypox in Nigeria, 2017. Emerging Infectious Diseases. 2018;24(6):1149–51. doi: 10.3201/eid2406.180017 WOS:000432430000036. 29619921

4. Reynolds MG, Doty JB, McCollum AM, Olson VA, Nakazawa Y. Monkeypox re-emergence in Africa: a call to expand the concept and practice of One Health. Expert Review of Anti-Infective Therapy. 2019;17(2):129–39. doi: 10.1080/14787210.2019.1567330 WOS:000457342000008. 30625020

5. Petersen E, Abubakar I, Ihekweazu C, Heymann D, Ntoumi F, Blumberg L, et al. Monkeypox—Enhancing public health preparedness for an emerging lethal human zoonotic epidemic threat in the wake of the smallpox post-eradication era. Int J Infect Dis. 2019;78:78–84. Epub 2018/11/20. doi: 10.1016/j.ijid.2018.11.008 30453097.

6. Reed KD, Melski JW, Graham MB, Regnery RL, Sotir MJ, Wegner MV, et al. The detection of monkeypox in humans in the Western Hemisphere. New Engl J Med. 2004;350(4):342–50. doi: 10.1056/NEJMoa032299 14736926

7. Likos AM, Sammons SA, Olson VA, Frace AM, Li Y, Olsen-Rasmussen M, et al. A tale of two clades: monkeypox viruses. J Gen Virol. 2005;86:2661–72. doi: 10.1099/vir.0.81215-0 16186219

8. Vaughan A, Aarons E, Astbury J, Balasegaram S, Beadsworth M, Beck CR, et al. Two cases of monkeypox imported to the United Kingdom, September 2018. Eurosurveillance. 2018;23(38):2–6. doi: 10.2807/1560-7917.Es.2018.23.38.1800509 WOS:000445123600001. 30255836

9. Jezek Z, Szczeniowski M, Paluku KM, Mutombo M. Human monkeypox: clinical features of 282 patients. J Infect Dis. 1987;156(2):293–8. Epub 1987/08/01. doi: 10.1093/infdis/156.2.293 3036967.

10. Nolen LD, Osadebe L, Katomba J, Likofata J, Mukadi D, Monroe B, et al. Extended Human-to-Human Transmission during a Monkeypox Outbreak in the Democratic Republic of the Congo. Emerging Infectious Diseases. 2016;22(6):1014–21. doi: 10.3201/eid2206.150579 WOS:000376794200009. 27191380

11. Weaver JR, Isaacs SN. Monkeypox virus and insights into its immunomodulatory proteins. Immunol Rev. 2008;225:96–113. ISI:000259344700007. doi: 10.1111/j.1600-065X.2008.00691.x 18837778

12. Hudson PN, Self J, Weiss S, Braden Z, Xiao YH, Girgis NM, et al. Elucidating the Role of the Complement Control Protein in Monkeypox Pathogenicity. Plos One. 2012;7(4). doi: e35086 WOS:000305014500044.

13. Johnson RF, Dyall J, Ragland DR, Huzella L, Byrum R, Jett C, et al. Comparative Analysis of Monkeypox Virus Infection of Cynomolgus Macaques by the Intravenous or Intrabronchial Inoculation Route. J Virol. 2011;85(5):2112–25. doi: 10.1128/JVI.01931-10 ISI:000286974900018. 21147922

14. Tesh RB, Watts DM, Sbrana E, Siirin M, Popov VL, Xiao SY. Experimental infection of ground squirrels (Spermophilius tridecemlineatus) with Monkeypox virus. Emerging Infect Dis. 2004;10(9):1563–7. doi: 10.3201/eid1009.040310 15498157

15. Sbrana E, Xiao SY, Newman PC, Tesh RB. Comparative pathology of North American and central African strains of monkeypox virus in a ground squirrel model of the disease. Amer J Trop Med Hyg. 2007;76(1):155–64.

16. Guarner J, Johnson BJ, Paddock CD, Shieh WJ, Goldsmith CS, Reynolds MG, et al. Monkeypox transmission and pathogenesis in prairie dogs. Emerging Infect Dis. 2004;10(3):426–31. doi: 10.3201/eid1003.030878 15109408

17. Langohr IM, Stevenson GW, Thacker HL, Regnery RL. Extensive lesions of Monkeypox in a prairie dog (Cynomys sp.). Vet Pathol. 2004;41(6):702–7. doi: 10.1354/vp.41-6-702 15557083

18. Xiao SY, Sbrana E, Watts DM, Siirin M, da RA, Tesh RB. Experimental infection of prairie dogs with monkeypox virus. Emerging Inf Dis. 2005;11(4):539–45.

19. Hutson CL, Olson VA, Carroll DS, Abel JA, Hughes CM, Braden ZH, et al. A prairie dog animal model of systemic orthopoxvirus disease using West African and Congo Basin strains of monkeypox virus. J Gen Virol. 2009;90(Pt 2):323–33. Epub 2009/01/15. 90/2/323 [pii] doi: 10.1099/vir.0.005108-0 19141441.

20. Schultz DA, Sagartz JE, Huso DL, Buller RML. Experimental infection of an African dormouse (Graphiurus kelleni) with monkeypox virus. Virology. 2009;383(1):86–92. doi: 10.1016/j.virol.2008.09.025 ISI:000262447300011. 18977501

21. Osorio JE, Iams KP, Meteyer CU, Rocke TE. Comparison of monkeypox viruses pathogenesis in mice by in vivo imaging. PLoS One. 2009;4(8):e6592. Epub 2009/08/12. doi: 10.1371/journal.pone.0006592 19668372.

22. Hutson CL, Abel JA, Carroll DS, Olson VA, Braden ZH, Hughes CM, et al. Comparison of West African and Congo Basin monkeypox viruses in BALB/c and C57BL/6 mice. PLoS One. 5(1):e8912. Epub 2010/01/30. doi: 10.1371/journal.pone.0008912 20111702.

23. Stabenow J, Buller RM, Schriewer J, West C, Sagartz JE, Parker S. A mouse model of lethal infection for evaluating prophylactics and therapeutics against monkeypox virus. J Virol. 2010;84(8):3909–20. doi: 10.1128/JVI.02012-09 ISI:000275781500018. 20130052

24. Americo JL, Moss B, Earl PL. Identification of wild-derived inbred mouse strains highly susceptible to monkeypox virus infection for use as small animal models. J Virol. 2010;84(16):8172–80. Epub 2010/06/04. JVI.00621-10 [pii] doi: 10.1128/JVI.00621-10 20519404.

25. Parker S, Buller RM. A review of experimental and natural infections of animals with monkeypox virus between 1958 and 2012. Future Virology. 2013;8(2):129–57. WOS:000314673200008. doi: 10.2217/fvl.12.130 23626656

26. Earl PL, Americo JL, Moss B. Genetic studies of the susceptibility of classical and wild-derived inbred mouse strains to monkeypox virus. Virology. 2015;481:161–5. doi: 10.1016/j.virol.2015.02.048 25791934.

27. Churchill GA, Airey DC, Allayee H, Angel JM, Attie AD, Beatty J, et al. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet. 2004;36(11):1133–7. Epub 2004/10/30. doi: 10.1038/ng1104-1133 15514660.

28. Threadgill DW, Miller DR, Churchill GA, de Villena FP. The collaborative cross: a recombinant inbred mouse population for the systems genetic era. ILAR journal / National Research Council, Institute of Laboratory Animal Resources. 2011;52(1):24–31. Epub 2011/03/18. doi: 10.1093/ilar.52.1.24 21411855.

29. Keane TM, Goodstadt L, Danecek P, White MA, Wong K, Yalcin B, et al. Mouse genomic variation and its effect on phenotypes and gene regulation. Nature. 2011;477(7364):289–94. doi: 10.1038/nature10413 21921910; PubMed Central PMCID: PMC3276836.

30. Americo JL, Sood CL, Cotter CA, Vogel JL, Kristie TM, Moss B, et al. Susceptibility of the wild-derived inbred CAST/Ei mouse to infection by orthopoxviruses analyzed by live bioluminescence imaging. Virology. 2014;449:120–32. WOS:000330094100014. doi: 10.1016/j.virol.2013.11.017 24418545

31. Leist SR, Pilzner C, van den Brand JM, Dengler L, Geffers R, Kuiken T, et al. Influenza H3N2 infection of the collaborative cross founder strains reveals highly divergent host responses and identifies a unique phenotype in CAST/EiJ mice. BMC Genomics. 2016;17:143. doi: 10.1186/s12864-016-2483-y 26921172; PubMed Central PMCID: PMC4769537.

32. Earl PL, Americo JL, Moss B. Lethal monkeypox virus infection of CAST/EiJ mice is associated with a deficient interferon-gamma response. J Virol. 2012;86:9105–12. Epub 2012/06/15. JVI.00162-12 [pii] doi: 10.1128/JVI.00162-12 22696658.

33. Earl PL, Americo JL, Moss B. Insufficient Innate Immunity Contributes to the Susceptibility of the Castaneous Mouse to Orthopoxvirus Infection. J Virol. 2017;91(19). doi: 10.1128/JVI.01042-17 28747505.

34. Burshtyn DN. NK cells and poxvirus infection. Front Immunol. 2013;4:7. doi: 10.3389/fimmu.2013.00007 23372568; PubMed Central PMCID: PMC3556567.

35. Mrozek E, Anderson P, Caligiuri MA. Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells. Blood. 1996;87(7):2632–40. Epub 1996/04/01. 8639878.

36. Carson WE, Fehniger TA, Haldar S, Eckhert K, Lindemann MJ, Lai CF, et al. A potential role for interleukin-15 in the regulation of human natural killer cell survival. J Clin Invest. 1997;99(5):937–43. Epub 1997/03/01. doi: 10.1172/JCI119258 9062351; PubMed Central PMCID: PMC507901.

37. Kennedy MK, Glaccum M, Brown SN, Butz EA, Viney JL, Embers M, et al. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med. 2000;191(5):771–80. doi: 10.1084/jem.191.5.771 10704459; PubMed Central PMCID: PMC2195858.

38. Ranson T, Vosshenrich CA, Corcuff E, Richard O, Muller W, Di Santo JP. IL-15 is an essential mediator of peripheral NK-cell homeostasis. Blood. 2003;101(12):4887–493. Epub 2003/02/15. doi: 10.1182/blood-2002-11-3392 12586624.

39. Verbist KC, Klonowski KD. Functions of IL-15 in anti-viral immunity: multiplicity and variety. Cytokine. 2012;59(3):467–78. Epub 2012/06/19. doi: 10.1016/j.cyto.2012.05.020 22704694; PubMed Central PMCID: PMC3422395.

40. Munger W, DeJoy SQ, Jeyaseelan R Sr., Torley LW, Grabstein KH, Eisenmann J, et al. Studies evaluating the antitumor activity and toxicity of interleukin-15, a new T cell growth factor: comparison with interleukin-2. Cell Immunol. 1995;165(2):289–93. Epub 1995/10/15. doi: 10.1006/cimm.1995.1216 7553894.

41. Evans R, Fuller JA, Christianson G, Krupke DM, Troutt AB. IL-15 mediates anti-tumor effects after cyclophosphamide injection of tumor-bearing mice and enhances adoptive immunotherapy: the potential role of NK cell subpopulations. Cell Immunol. 1997;179(1):66–73. Epub 1997/07/10. doi: 10.1006/cimm.1997.1132 9259773.

42. Collin R, Balmer L, Morahan G, Lesage S. Common Heritable Immunological Variations Revealed in Genetically Diverse Inbred Mouse Strains of the Collaborative Cross. J Immunol. 2019;202(3):777–86. Epub 2018/12/28. doi: 10.4049/jimmunol.1801247 30587532.

43. Earl PL, Americo JL, Cotter CA, Moss B. Comparative live bioluminescence imaging of monkeypox virus dissemination in a wild-derived inbred mouse (Mus musculus castaneus) and outbred African dormouse (Graphiurus kelleni). Virology. 2015;475:150–8. doi: 10.1016/j.virol.2014.11.015 25462355; PubMed Central PMCID: PMC4280325.

44. Xu R, Johnson AJ, Liggitt D, Bevan MJ. Cellular and humoral immunity against vaccinia virus infection of mice. J Immunol. 2004;172(10):6265–71. doi: 10.4049/jimmunol.172.10.6265 15128815

45. Lodolce JP, Boone DL, Chai S, Swain RE, Dassopoulos T, Trettin S, et al. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity. 1998;9(5):669–76. Epub 1998/12/10. doi: 10.1016/s1074-7613(00)80664-0 9846488.

46. Carson WE, Dierksheide JE, Jabbour S, Anghelina M, Bouchard P, Ku G, et al. Coadministration of interleukin-18 and interleukin-12 induces a fatal inflammatory response in mice: critical role of natural killer cell interferon-gamma production and STAT-mediated signal transduction. Blood. 2000;96(4):1465–73. Epub 2000/08/15. 10942393.

47. Roda JM, Parihar R, Magro C, Nuovo GJ, Tridandapani S, Carson WE, 3rd. Natural killer cells produce T cell-recruiting chemokines in response to antibody-coated tumor cells. Cancer Res. 2006;66(1):517–26. Epub 2006/01/07. doi: 10.1158/0008-5472.CAN-05-2429 16397268.

48. Goh W, Huntington ND. Regulation of Murine Natural Killer Cell Development. Front Immunol. 2017;8:130. Epub 2017/03/07. doi: 10.3389/fimmu.2017.00130 28261203; PubMed Central PMCID: PMC5309223.

49. Nakahira M, Ahn HJ, Park WR, Gao P, Tomura M, Park CS, et al. Synergy of IL-12 and IL-18 for IFN-gamma gene expression: IL-12-induced STAT4 contributes to IFN-gamma promoter activation by up-regulating the binding activity of IL-18-induced activator protein 1. J Immunol. 2002;168(3):1146–53. Epub 2002/01/22. doi: 10.4049/jimmunol.168.3.1146 11801649.

50. Gherardi MM, Ramirez JC, Esteban M. IL-12 and IL-18 act in synergy to clear vaccinia virus infection: involvement of innate and adaptive components of the immune system. Journal of General Virology. 2003;84:1961–72. doi: 10.1099/vir.0.19120-0 12867626

51. Freeman BE, Raue HP, Hill AB, Slifka MK. Cytokine-Mediated Activation of NK Cells during Viral Infection. J Virol. 2015;89(15):7922–31. Epub 2015/05/23. doi: 10.1128/JVI.00199-15 25995253; PubMed Central PMCID: PMC4505636.

52. Reading PC, Smith GL. Vaccinia virus interleukin-18-binding protein promotes virulence by reducing gamma interferon production and natural killer and T-cell activity. J Virol. 2003;77(18):9960–8. doi: 10.1128/JVI.77.18.9960-9968.2003 12941906

53. Petkova SB, Yuan R, Tsaih SW, Schott W, Roopenian DC, Paigen B. Genetic influence on immune phenotype revealed strain-specific variations in peripheral blood lineages. Physiol Genomics. 2008;34(3):304–14. Epub 2008/06/12. doi: 10.1152/physiolgenomics.00185.2007 18544662; PubMed Central PMCID: PMC2519960.

54. Huntington ND. The unconventional expression of IL-15 and its role in NK cell homeostasis. Immunol Cell Biol. 2014;92(3):210–3. doi: 10.1038/icb.2014.1 24492800.

55. Cooper MA, Bush JE, Fehniger TA, VanDeusen JB, Waite RE, Liu Y, et al. In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood. 2002;100(10):3633–8. Epub 2002/10/24. doi: 10.1182/blood-2001-12-0293 12393617.

56. Koka R, Burkett PR, Chien M, Chai S, Chan F, Lodolce JP, et al. Interleukin (IL)-15R[alpha]-deficient natural killer cells survive in normal but not IL-15R[alpha]-deficient mice. J Exp Med. 2003;197(8):977–84. Epub 2003/04/16. doi: 10.1084/jem.20021836 12695489; PubMed Central PMCID: PMC2193874.

57. Townsley AC, Weisberg AS, Wagenaar TR, Moss B. Vaccinia virus entry into cells via a low pH-dependent-endosomal pathway. J Virol. 2006;80:8899–908. doi: 10.1128/JVI.01053-06 16940502

58. Cotter CA, Earl PL, Wyatt LS, Moss B. Preparation of cell cultures and vaccinia virus stocks. Curr Protoc Microbiol. 2015;39:14A 3 1–8. doi: 10.1002/9780471729259.mc14a03s39 26528781.

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