Skip to main content
Book cover

Inflammation pp 121–136Cite as

Murine Models of Allergic Asthma

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1559))

Abstract

Allergic asthma is a heterogeneous inflammatory lung disease affecting millions of people worldwide and with a steadily increasing incidence. Mouse models have been of utmost importance in uncovering key inflammatory cell types, cytokines, and pathways in the development and maintenance of allergic asthma. Historically, the mainstay in experimental asthma research was sensitizing rodents to the model protein antigen ovalbumin (OVA) with the pro-Th2 adjuvant aluminum hydroxide, followed by repetitive OVA exposures to the airways to initiate a Th2-skewed adaptive immune response leading to eosinophilic airway inflammation and airway hyperreactivity (AHR). In the last 5 years, OVA is often replaced by naturally occurring allergens such as house dust mite (HDM) or cockroach extracts, but the principle of first sensitizing and then repetitively challenging mice with the same antigen is unchanged. Here, we describe an often used and relevant HDM-based protocol to establish acute allergic asthma, and the methods we have developed to rapidly analyze inflammatory cell infiltration in the bronchalveolar lavage fluid by flow cytometry. Moreover, we explain the methods to restimulate T cells from lung-draining mediastinal lymph nodes with HDM to allow the measurement of cytokine secretion profiles of allergen reactive T cells.

This is a preview of subscription content, log in via an institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Robinson DS, Qutayba H, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay B (1992) Predominant Th2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 326(5):298–304

    Article  CAS  PubMed  Google Scholar 

  2. Holgate ST, Polosa R (2008) Treatment strategies for allergy and asthma. Nat Rev Immunol 8:218–230. doi:10.1038/nri2262

    Article  CAS  PubMed  Google Scholar 

  3. Barnes PJ (2011) Glucocorticosteroids: current and future directions. Br J Pharmacol 163:29–43. doi:10.1111/j.1476-5381.2010.01199.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kumar RK, Herbert C, Foster PS (2008) The “classical” ovalbumin challenge model of asthma in mice. Curr Drug Targets 9:485–494. doi:10.2174/138945008784533561

    Article  CAS  PubMed  Google Scholar 

  5. Corry DB, Grünig G, Hadeiba H, Kurup VP, Warnock ML, Sheppard D, Rennick DM, Locksley RM (1998) Requirements for allergen-induced airway hyperreactivity in T and B cell-deficient mice. Mol Med 4:344–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Corry DB, Folkesson HG, Warnock ML, Erle DJ, Matthay MA, Wiener-Kronish JP, Locksley RM (1996) Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J Exp Med 183:109–117. doi:10.1084/jem.183.1.109

    Article  CAS  PubMed  Google Scholar 

  7. Mould AW, Ramsay AJ, Matthaei KI, Young IG, Rothenberg ME, Foster PS (2000) The effect of IL-5 and eotaxin expression in the lung on eosinophil trafficking and degranulation and the induction of bronchial hyperreactivity. J Immunol 164:2142–2150, ji_v164n4p2142 [pii]

    Article  CAS  PubMed  Google Scholar 

  8. Ingram JL, Kraft M (2012) IL-13 in asthma and allergic disease: asthma phenotypes and targeted therapies. J Allergy Clin Immunol 130:829–842. doi:10.1016/j.jaci.2012.06.034

    Article  CAS  PubMed  Google Scholar 

  9. Lambrecht BN, Salomon B, Klatzmann D, Pauwels RA (1998) Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J Immunol 160:4090–4097

    CAS  PubMed  Google Scholar 

  10. Lambrecht BN, Peleman RA, Bullock GR, Pauwels RA (2000) Sensitization to inhaled antigen by intratracheal instillation of dendritic cells. Clin Exp Allergy 30:214–224, cea818 [pii]

    Article  CAS  PubMed  Google Scholar 

  11. Kool M, Soullié T, van Nimwegen M, Willart MAM, Muskens F, Jung S, Hoogsteden HC, Hammad H, Lambrecht BN (2008) Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med 205:869–882. doi:10.1084/jem.20071087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Borish LC, Nelson HS, Lanz MJ, Claussen L, Whitmore JB, Agosti JM, Garrison L (1999) Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med 160:1816–1823

    Article  CAS  PubMed  Google Scholar 

  13. Kips JC, O’Connor BJ, Langley SJ, Woodcock A, Kerstjens HAM, Postma DS, Danzig M, Cuss F, Pauwels RA (2003) Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med 167:1655–1659. doi:10.1164/rccm.200206-525OC

    Article  PubMed  Google Scholar 

  14. Leckie MJ, Ten Brinke A, Khan J, Diamant Z, O’Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ (2000) Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356:2144–2148. doi:10.1016/S0140-6736(00)03496-6

    Article  CAS  PubMed  Google Scholar 

  15. Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K (2002) Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J Exp Med 196:1645–1651. doi:10.1084/jem.20021340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jacquet A (2011) The role of innate immunity activation in house dust mite allergy. Trends Mol Med 17:604–611. doi:10.1016/j.molmed.2011.05.014

    Article  CAS  PubMed  Google Scholar 

  17. Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN (2009) House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 15:410–416. doi:10.1038/nm.1946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. McMillan SJ, Lloyd CM (2004) Prolonged allergen challenge in mice leads to persistent airway remodelling. Clin Exp Allergy 34:497–507. doi:10.1111/j.1365-2222.2004.01895.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Martin RA, Hodgkins SR, Dixon AE, Poynter ME (2014) Aligning mouse models of asthma to human endotypes of disease. Respirology 19:823–833. doi:10.1111/resp.12315

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kelada SNP, Wilson MS, Tavarez U, Kubalanza K, Borate B, Whitehead GS, Maruoka S, Roy MG, Olive M, Carpenter DE, Brass DM, Wynn TA, Cook DN, Evans CM, Schwartz DA, Collins FS (2011) Strain-dependent genomic factors affect allergen-induced airway hyperresponsiveness in mice. Am J Respir Cell Mol Biol 45:817–824. doi:10.1165/rcmb.2010-0315OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Morokata T, Ishikawa J, Ida K, Yamada T (1999) C57BL/6 mice are more susceptible to antigen-induced pulmonary eosinophilia than BALB/c mice, irrespective of systemic T helper 1/T helper 2 responses. Immunology 98:345–351. doi:10.1046/j.1365-2567.1999.00890.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Van Hove CL, Maes T, Cataldo DD, Guéders MM, Palmans E, Joos GF, Tournoy KG (2009) Comparison of acute inflammatory and chronic structural asthma-like responses between C57BL/6 and BALB/c Mice. Int Arch Allergy Immunol 149:195–207. doi:10.1159/000199715

    Article  PubMed  Google Scholar 

  23. 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 305:1773–1776. doi:10.1126/science.1099472

    Article  CAS  PubMed  Google Scholar 

  24. 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 305:1776–1779. doi:10.1126/science.1100283

    Article  CAS  PubMed  Google Scholar 

  25. Hadeiba H, Corry DB, Locksley RM (2000) Baseline airway hyperreactivity in A/J mice is not mediated by cells of the adaptive immune system. J Immunol 164:4933–4940, ji_v164n9p4933 [pii]

    Article  CAS  PubMed  Google Scholar 

  26. Hadebe S, Kirstein F, Fierens K, Chen K, Drummond RA, Vautier S, Sajaniemi S, Murray G, Williams DL, Redelinghuys P, Reinhart TA, Fallert Junecko BA, Kolls JK, Lambrecht BN, Brombacher F, Brown GD (2015) Microbial ligand costimulation drives neutrophilic steroid-refractory asthma. PLoS One 10:e0134219. doi:10.1371/journal.pone.0134219

    Article  PubMed  PubMed Central  Google Scholar 

  27. Schuijs MJ, Willart MA, Vergote K, Grad D, Deswarte K, Ege MJ, Madeira FB, Beyaert R (2015) Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science 349:1907–1911

    Article  Google Scholar 

  28. Plantinga M, Guilliams M, Vanheerswynghels M, Deswarte K, Branco-Madeira F, Toussaint W, Vanhoutte L, Neyt K, Killeen N, Malissen B, Hammad H, Lambrecht BN (2013) Conventional and monocyte-derived CD11b + dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. Immunity 38:322–335. doi:10.1016/j.immuni.2012.10.016

    Article  CAS  PubMed  Google Scholar 

  29. Walzer T, Brawand P, Swart D, Tocker J, De Smedt T (2005) No defect in T-cell priming, secondary response, or tolerance induction in response to inhaled antigens in Fms-like tyrosine kinase 3 ligand-deficient mice. J Allergy Clin Immunol 115:192–199. doi:10.1016/j.jaci.2004.08.046

    Article  CAS  PubMed  Google Scholar 

  30. Kobayashi T, Miura T, Haba T, Sato M, Serizawa I, Nagai H, Ishizaka K (2000) An essential role of mast cells in the development of airway hyperresponsiveness in a murine asthma model. J Immunol 164:3855–3861. doi:10.4049/jimmunol.164.7.3855

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Eline Haspeslagh is supported by the Research Foundation Flanders (FWO).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bart N. Lambrecht .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Haspeslagh, E., Debeuf, N., Hammad, H., Lambrecht, B.N. (2017). Murine Models of Allergic Asthma. In: Clausen, B., Laman, J. (eds) Inflammation. Methods in Molecular Biology, vol 1559. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6786-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6786-5_10

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6784-1

  • Online ISBN: 978-1-4939-6786-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics