Th9 Cells pp 223-245

Part of the Methods in Molecular Biology book series (MIMB, volume 1585) | Cite as

Th9 Cells and Parasitic Inflammation: Use of Nippostrongylus and Schistosoma Models

  • Miguel Enrique Serrano Pinto
  • Paula Licona-Limón
Protocol

Abstract

Th9 cells are a new subpopulation of CD4+ T helper cells, characterized by the expression of IL-9 that have been involved in type 2 immune responses, antitumor responses and autoimmune diseases. Here, we describe two different parasitic models frequently maintained in the laboratory where Th9 cells or IL-9 (the cytokine produced by Th9 cells) has been shown to play critical roles in pathogen clearance and immune response activation: the nematode Nippostrongylus brasiliensis and the trematode Schistosoma mansoni.

Key words

IL-9 Type 2 immune response Helminth Th9 Parasite infection 

References

  1. 1.
    Lukacs NW, Strieter RM, Kunkel SL (1995) Leukocyte infiltration in allergic airway inflammation. Am J Respir Cell Mol Biol 13(1):1–6. doi:10.1165/ajrcmb.13.1.7598934 CrossRefPubMedGoogle Scholar
  2. 2.
    Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB (1992) Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 326(5):298–304. doi:10.1056/NEJM199201303260504 CrossRefPubMedGoogle Scholar
  3. 3.
    Wilhelm C, Hirota K, Stieglitz B, Van Snick J, Tolaini M, Lahl K, Sparwasser T, Helmby H, Stockinger B (2011) An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation. Nat Immunol 12(11):1071–1077. doi:10.1038/ni.2133 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Licona-Limon P, Henao-Mejia J, Temann AU, Gagliani N, Licona-Limon I, Ishigame H, Hao L, Herbert DR, Flavell RA (2013) Th9 Cells Drive Host Immunity against Gastrointestinal Worm Infection. Immunity 39(4):744–757. doi:10.1016/j.immuni.2013.07.020 CrossRefPubMedGoogle Scholar
  5. 5.
    Nicolaides NC, Holroyd KJ, Ewart SL, Eleff SM, Kiser MB, Dragwa CR, Sullivan CD, Grasso L, Zhang LY, Messler CJ, Zhou T, Kleeberger SR, Buetow KH, Levitt RC (1997) Interleukin 9: a candidate gene for asthma. Proc Natl Acad Sci U S A 94(24):13175–13180CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Levitt RC, McLane MP, MacDonald D, Ferrante V, Weiss C, Zhou T, Holroyd KJ, Nicolaides NC (1999) IL-9 pathway in asthma: new therapeutic targets for allergic inflammatory disorders. J Allergy Clin Immunol 103(5 Pt 2):S485–S491CrossRefPubMedGoogle Scholar
  7. 7.
    Faulkner H, Renauld JC, Van Snick J, Grencis RK (1998) Interleukin-9 enhances resistance to the intestinal nematode Trichuris muris. Infect Immun 66(8):3832–3840PubMedPubMedCentralGoogle Scholar
  8. 8.
    Uyttenhove C, Simpson RJ, Van Snick J (1988) Functional and structural characterization of P40, a mouse glycoprotein with T-cell growth factor activity. Proc Natl Acad Sci U S A 85(18):6934–6938CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Petit-Frere C, Dugas B, Braquet P, Mencia-Huerta JM (1993) Interleukin-9 potentiates the interleukin-4-induced IgE and IgG1 release from murine B lymphocytes. Immunology 79(1):146–151PubMedPubMedCentralGoogle Scholar
  10. 10.
    Dugas B, Renauld JC, Pene J, Bonnefoy JY, Peti-Frere C, Braquet P, Bousquet J, Van Snick J, Mencia-Huerta JM (1993) Interleukin-9 potentiates the interleukin-4-induced immunoglobulin (IgG, IgM and IgE) production by normal human B lymphocytes. Eur J Immunol 23(7):1687–1692. doi:10.1002/eji.1830230743 CrossRefPubMedGoogle Scholar
  11. 11.
    Shimbara A, Christodoulopoulos P, Soussi-Gounni A, Olivenstein R, Nakamura Y, Levitt RC, Nicolaides NC, Holroyd KJ, Tsicopoulos A, Lafitte JJ, Wallaert B, Hamid QA (2000) IL-9 and its receptor in allergic and nonallergic lung disease: increased expression in asthma. J Allergy Clin Immunol 105(1 Pt 1):108–115CrossRefPubMedGoogle Scholar
  12. 12.
    Schmitt E, Germann T, Goedert S, Hoehn P, Huels C, Koelsch S, Kuhn R, Muller W, Palm N, Rude E (1994) IL-9 production of naive CD4+ T cells depends on IL-2, is synergistically enhanced by a combination of TGF-beta and IL-4, and is inhibited by IFN-gamma. J Immunol 153(9):3989–3996PubMedGoogle Scholar
  13. 13.
    Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, Buer J, Martin B, Wilhelm C, Stockinger B (2008) Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 9(12):1341–1346. doi:10.1038/ni.1659 CrossRefPubMedGoogle Scholar
  14. 14.
    Dardalhon V, Awasthi A, Kwon H, Galileos G, Gao W, Sobel RA, Mitsdoerffer M, Strom TB, Elyaman W, Ho IC, Khoury S, Oukka M, Kuchroo VK (2008) IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(−) effector T cells. Nat Immunol (12):1347–1355. doi:10.1038/ni.1677
  15. 15.
    Purwar R, Schlapbach C, Xiao S, Kang HS, Elyaman W, Jiang X, Jetten AM, Khoury SJ, Fuhlbrigge RC, Kuchroo VK, Clark RA, Kupper TS (2012) Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells. Nat Med 18(8):1248–1253. doi:10.1038/nm.2856 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Jager A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK (2009) Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 183(11):7169–7177. doi:10.4049/jimmunol.0901906 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Gerlach K, Hwang Y, Nikolaev A, Atreya R, Dornhoff H, Steiner S, Lehr HA, Wirtz S, Vieth M, Waisman A, Rosenbauer F, McKenzie AN, Weigmann B, Neurath MF (2014) TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells. Nat Immunol 15(7):676–686. doi:10.1038/ni.2920 CrossRefPubMedGoogle Scholar
  18. 18.
    Ciccia F, Guggino G, Rizzo A, Manzo A, Vitolo B, La Manna MP, Giardina G, Sireci G, Dieli F, Montecucco CM, Alessandro R, Triolo G (2015) Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 54(12):2264–2272. doi:10.1093/rheumatology/kev252 CrossRefGoogle Scholar
  19. 19.
    Kennedy MWHW (2013) Parasitic nematodes: molecular biology, biochemistry and immunology, 2nd edn. CAB International, Wallingford CrossRefGoogle Scholar
  20. 20.
    Organization WH (2016) Soil transmitted helminth infections. WHO Media Center, GenevaGoogle Scholar
  21. 21.
    Urban JF Jr, Maliszewski CR, Madden KB, Katona IM, Finkelman FD (1995) IL-4 treatment can cure established gastrointestinal nematode infections in immunocompetent and immunodeficient mice. J Immunol 154(9):4675–4684PubMedGoogle Scholar
  22. 22.
    Barner M, Mohrs M, Brombacher F, Kopf M (1998) Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses. Curr Biol 8(11):669–672CrossRefPubMedGoogle Scholar
  23. 23.
    McKenzie GJ, Emson CL, Bell SE, Anderson S, Fallon P, Zurawski G, Murray R, Grencis R, McKenzie AN (1998) Impaired development of Th2 cells in IL-13-deficient mice. Immunity 9(3):423–432CrossRefPubMedGoogle Scholar
  24. 24.
    WHO (2016) Schistosomiasis Media center fact sheet. WHO, GenevaGoogle Scholar
  25. 25.
    Schramm G, Haas H (2010) Th2 immune response against Schistosoma mansoni infection. Microbes Infect 12(12–13):881–888. doi:10.1016/j.micinf.2010.06.001 CrossRefPubMedGoogle Scholar
  26. 26.
    Fallon PG, Smith P, Dunne DW (1998) Type 1 and type 2 cytokine-producing mouse CD4+ and CD8+ T cells in acute Schistosoma mansoni infection. Eur J Immunol 28(4):1408–1416CrossRefPubMedGoogle Scholar
  27. 27.
    Khalil RM, Luz A, Mailhammer R, Moeller J, Mohamed AA, Omran S, Dormer P, Hultner L (1996) Schistosoma mansoni infection in mice augments the capacity for interleukin 3 (IL-3) and IL-9 production and concurrently enlarges progenitor pools for mast cells and granulocytes-macrophages. Infect Immun 64(12):4960–4966PubMedPubMedCentralGoogle Scholar
  28. 28.
    Fallon PG, Smith P, Richardson EJ, Jones FJ, Faulkner HC, Van Snick J, Renauld JC, Grencis RK, Dunne DW (2000) Expression of interleukin-9 leads to Th2 cytokine-dominated responses and fatal enteropathy in mice with chronic Schistosoma mansoni infections. Infect Immun 68(10):6005–6011CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Townsend JM, Fallon GP, Matthews JD, Smith P, Jolin EH, McKenzie NA (2000) IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity 13(4):573–583CrossRefPubMedGoogle Scholar
  30. 30.
    Camberis M, Le Gros G, Urban J Jr (2003) Animal model of Nippostrongylus brasiliensis and Heligmosomoides polygyrus. Curr Protoc Immunol Chapter 19:Unit 19.12. doi:10.1002/0471142735.im1912s55 PubMedGoogle Scholar
  31. 31.
    Lewis FA (1998) Schistosomiasis. Current protocols in immunology. Jonh Wiley & Sons inc, New York, NYGoogle Scholar
  32. 32.
    Nawa Y, Miller HR, Hall E, Jarrett EE (1981) Adoptive transfer of total and parasite-specific IgE responses in rats infected with Nippostrongylus brasiliensis. Immunology 44(1):119–123PubMedPubMedCentralGoogle Scholar
  33. 33.
    SM A (1997) Dialisis and concentration of protein solutions. Current protocols in immunology. Jonh Wiley & Sons inc, New York, NYGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Miguel Enrique Serrano Pinto
    • 1
  • Paula Licona-Limón
    • 1
  1. 1.Departamento de Biología Celular y del DesarrolloInstituto de Fisiología Celular, Universidad Nacional Autónoma de MéxicoMexico CityMexico

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