Advertisement

Eosinophils pp 295-308 | Cite as

Mutant Mice and Animal Models of Airway Allergic Disease

  • Marie-Renée BlanchetEmail author
  • Matthew Gold
  • Kelly M. McNagny
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1178)

Abstract

Eosinophilia is a hallmark of allergic airway inflammation, and eosinophils represent an integral effector leukocyte through their release of various granule-stored cytokines and proteins. Numerous mouse models have been developed to mimic clinical disease and they have been instrumental in furthering our understanding of the role of eosinophils in disease. Most of these models consist of intranasal (i.n.) administration of antigenic proteases including papain and house dust mite (HDM) or the neo-antigen ovalbumin, with a resulting Th2-biased immune response and airway eosinophilia. These models have been particularly informative when combined with the numerous transgenic mice available that modulate eosinophil frequency or the mechanisms involved in their migration. Here, we describe the current models or allergic airway inflammation and outline some of the transgenic mice available to study eosinophils in disease.

Key words

Asthma Inflammation Eosinophil Mouse 

References

  1. 1.
    Barnes PJ (2008) Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 8:183–192PubMedCrossRefGoogle Scholar
  2. 2.
    Phipps S, Lam CE, Kaiko GE, Foo SY, Collison A, Mattes J, Barry J, Davidson S, Oreo K, Smith L, Mansell A, Matthaei KI, Foster PS (2009) Toll/IL-1 signaling is critical for house dust mite-specific helper T cell type 2 and type 17 [corrected] responses. Am J Respir Crit Care Med 179:883–893PubMedCrossRefGoogle Scholar
  3. 3.
    Soto-Mera MT, Lopez-Rico MR, Filgueira JF, Villamil E, Cidras R (2000) Occupational allergy to papain. Allergy 55:983–984PubMedCrossRefGoogle Scholar
  4. 4.
    Blanchet MR, Maltby S, Haddon DJ, Merkens H, Zbytnuik L, McNagny KM (2007) CD34 facilitates the development of allergic asthma. Blood 110:2005–2012PubMedCrossRefGoogle Scholar
  5. 5.
    Jacobsen EA, Helmers RA, Lee JJ, Lee NA (2012) The expanding role(s) of eosinophils in health and disease. Blood 120:3882–3890PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Lee JJ, Dimina D, Macias MP, Ochkur SI, McGarry MP, O'Neill KR, Protheroe C, Pero R, Nguyen T, Cormier SA, Lenkiewicz E, Colbert D, Rinaldi L, Ackerman SJ, Irvin CG, Lee NA (2004) Defining a link with asthma in mice congenitally deficient in eosinophils. Science 305:1773–1776PubMedCrossRefGoogle Scholar
  7. 7.
    Humbles AA, Lloyd CM, McMillan SJ, Friend DS, Xanthou G, McKenna EE, Ghiran S, Gerard NP, Yu C, Orkin SH, Gerard C (2004) A critical role for eosinophils in allergic airways remodeling. Science 305:1776–1779PubMedCrossRefGoogle Scholar
  8. 8.
    Blanchet MR, Gold M, Maltby S, Bennett J, Petri B, Kubes P, Lee DM, McNagny KM (2010) Loss of CD34 leads to exacerbated autoimmune arthritis through increased vascular permeability. J Immunol 184:1292–1299PubMedCrossRefGoogle Scholar
  9. 9.
    Walsh ER, Sahu N, Kearley J, Benjamin E, Kang BH, Humbles A, August A (2008) Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma. J Exp Med 205:1285–1292PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Doyle AD, Jacobsen EA, Ochkur SI, Willetts L, Shim K, Neely J, Kloeber J, Lesuer WE, Pero RS, Lacy P, Moqbel R, Lee NA, Lee JJ (2013) Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils. J Leukoc Biol 94:17–24PubMedCrossRefGoogle Scholar
  11. 11.
    Blanchet MR, Bennett JL, Gold MJ, Levantini E, Tenen DG, Girard M, Cormier Y, McNagny KM (2011) CD34 is required for dendritic cell trafficking and pathology in murine hypersensitivity pneumonitis. Am J Respir Crit Care Med 184:687–698PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Drew E, Merkens H, Chelliah S, Doyonnas R, McNagny KM (2002) CD34 is a specific marker of mature murine mast cells. Exp Hematol 30:1211–1218PubMedCrossRefGoogle Scholar
  13. 13.
    Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa J, Ohtani M, Fujii H, Koyasu S (2010) Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 463:540–544PubMedCrossRefGoogle Scholar
  14. 14.
    Halim TY, Krauss RH, Sun AC, Takei F (2012) Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation. Immunity 36:451–463PubMedCrossRefGoogle Scholar
  15. 15.
    Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TK, Bucks C, Kane CM, Fallon PG, Pannell R, Jolin HE, McKenzie AN (2010) Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464:1367–1370PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Yasuda K, Muto T, Kawagoe T, Matsumoto M, Sasaki Y, Matsushita K, Taki Y, Futatsugi-Yumikura S, Tsutsui H, Ishii KJ, Yoshimoto T, Akira S, Nakanishi K (2012) Contribution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode-infected mice. Proc Natl Acad Sci U S A 109:3451–3456PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, Chawla A, Locksley RM (2013) Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med 210:535–549PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Barlow JL, Bellosi A, Hardman CS, Drynan LF, Wong SH, Cruickshank JP, McKenzie AN (2012) Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity. J Allergy Clin Immunol 129(191–198): e191–e194CrossRefGoogle Scholar
  19. 19.
    Klein Wolterink RG, Serafini N, van Nimwegen M, Vosshenrich CA, de Bruijn MJ, Fonseca Pereira D, Veiga Fernandes H, Hendriks RW, Di Santo JP (2013) Essential, dose-dependent role for the transcription factor Gata3 in the development of IL-5+ and IL-13+ type 2 innate lymphoid cells. Proc Natl Acad Sci U S A 110:10240–10245PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Hoyler T, Klose CS, Souabni A, Turqueti-Neves A, Pfeifer D, Rawlins EL, Voehringer D, Busslinger M, Diefenbach A (2012) The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity 37:634–648PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Yang Q, Monticelli LA, Saenz SA, Chi AW, Sonnenberg GF, Tang J, De Obaldia ME, Bailis W, Bryson JL, Toscano K, Huang J, Haczku A, Pear WS, Artis D, Bhandoola A (2013) T cell factor 1 is required for group 2 innate lymphoid cell generation. Immunity 38:694–704PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Wong SH, Walker JA, Jolin HE, Drynan LF, Hams E, Camelo A, Barlow JL, Neill DR, Panova V, Koch U, Radtke F, Hardman CS, Hwang YY, Fallon PG, McKenzie AN (2012) Transcription factor RORalpha is critical for nuocyte development. Nat Immunol 13:229–236PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Halim TY, MacLaren A, Romanish MT, Gold MJ, McNagny KM, Takei F (2012) Retinoic-acid-receptor-related orphan nuclear receptor alpha is required for natural helper cell development and allergic inflammation. Immunity 37:463–474PubMedCrossRefGoogle Scholar
  24. 24.
    Naus S, Blanchet MR, Gossens K, Zaph C, Bartsch JW, McNagny KM, Ziltener HJ (2010) The metalloprotease-disintegrin ADAM8 is essential for the development of experimental asthma. Am J Respir Crit Care Med 181:1318–1328PubMedCrossRefGoogle Scholar
  25. 25.
    Blanchet MR, Israel-Assayag E, Cormier Y (2005) Modulation of airway inflammation and resistance in mice by a nicotinic receptor agonist. Eur Respir J 26:21–27PubMedCrossRefGoogle Scholar
  26. 26.
    Haddon DJ, Antignano F, Hughes MR, Blanchet MR, Zbytnuik L, Krystal G, McNagny KM (2009) SHIP1 is a repressor of mast cell hyperplasia, cytokine production, and allergic inflammation in vivo. J Immunol 183:228–236PubMedCrossRefGoogle Scholar
  27. 27.
    O'Brien R, Ooi MA, Clarke AH, Thomas WR (1996) Immunologic responses following respiratory sensitization to house dust mite allergens in mice. Immunol Cell Biol 74:174–179PubMedCrossRefGoogle Scholar
  28. 28.
    Thomas WR, Smith WA, Hales BJ, Mills KL, O'Brien RM (2002) Characterization and immunobiology of house dust mite allergens. Int Arch Allergy Immunol 129:1–18PubMedCrossRefGoogle Scholar
  29. 29.
    Jarman ER, Tan KA, Lamb JR (2005) Transgenic mice expressing the T cell antigen receptor specific for an immunodominant epitope of a major allergen of house dust mite develop an asthmatic phenotype on exposure of the airways to allergen. Clin Exp Allergy 35:960–969PubMedCrossRefGoogle Scholar
  30. 30.
    Milne J, Brand S (1975) Occupational asthma after inhalation of dust of the proteolytic enzyme, papain. Br J Ind Med 32:302–307PubMedCentralPubMedGoogle Scholar
  31. 31.
    Sokol CL, Barton GM, Farr AG, Medzhitov R (2008) A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat Immunol 9:310–318PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Oboki K, Ohno T, Kajiwara N, Arae K, Morita H, Ishii A, Nambu A, Abe T, Kiyonari H, Matsumoto K, Sudo K, Okumura K, Saito H, Nakae S (2010) IL-33 is a crucial amplifier of innate rather than acquired immunity. Proc Natl Acad Sci U S A 107:18581–18586PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Joshi AD, Fong DJ, Oak SR, Trujillo G, Flaherty KR, Martinez FJ, Hogaboam CM (2009) Interleukin-17-mediated immunopathogenesis in experimental hypersensitivity pneumonitis. Am J Respir Crit Care Med 179:705–716PubMedCrossRefGoogle Scholar
  34. 34.
    Gudmundsson G, Hunninghake GW (1997) Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis. J Clin Invest 99:2386–2390PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Girard M, Cormier Y (2010) Hypersensitivity pneumonitis. Curr Opin Allergy Clin Immunol 10:99–103PubMedCrossRefGoogle Scholar
  36. 36.
    Melgert BN, Oriss TB, Qi Z, Dixon-McCarthy B, Geerlings M, Hylkema MN, Ray A (2010) Macrophages: regulators of sex differences in asthma? Am J Respir Cell Mol Biol 42:595–603PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Melgert BN, Postma DS, Kuipers I, Geerlings M, Luinge MA, van der Strate BW, Kerstjens HA, Timens W, Hylkema MN (2005) Female mice are more susceptible to the development of allergic airway inflammation than male mice. Clin Exp Allergy 35:1496–1503PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, New York 2014

Authors and Affiliations

  • Marie-Renée Blanchet
    • 1
    Email author
  • Matthew Gold
    • 2
  • Kelly M. McNagny
    • 2
  1. 1.Centre de RechercheInstitut Universitaire de Cardiologie et de Pneumologie de QuébecQuébecCanada
  2. 2.The Biomedical Research CentreUniversity of British ColumbiaVancouverCanada

Personalised recommendations