Abstract
Animal models can be helpful tools for deciphering the generation, maintenance, and role of tertiary lymphoid structures (TLS) during infections or tumor development. We describe here the establishment of a persistent lung infection in immune-competent mice by intratracheal instillation of agarose beads containing Pseudomonas aeruginosa or Staphylococcus aureus bacteria. After instillation, animals develop a chronic pulmonary infection, marked by the presence of TLS. This experimental setting allows the study of the function of TLS induced by bacteria encountered in patients with cystic fibrosis (CF) as P. aeruginosa and S. aureus are the two main bacterial strains that infect bronchi of adult CF patients. Additionally, we describe also how to manipulate the immune response in these infected animals by targeting immune cells involved in TLS function. Overall, this approach makes it possible to explore the role of chronic inflammation in the induction and maintenance of TLS in infected tissues.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bienenstock J, Johnston N, Perey DY (1973) Bronchial lymphoid tissue. I. Morphologic characteristics. Lab Investig 28:686–692
Bienenstock J, Johnston N, Perey DY (1973) Bronchial lymphoid tissue. II. Functional characteristics. Lab Invest 28:693–698
Pabst R, Gehrke I (1990) Is the bronchus-associated lymphoid tissue (BALT) an integral structure of the lung in normal mammals, including humans? Am J Respir Cell Mol Biol 3:131–135. https://doi.org/10.1165/ajrcmb/3.2.131
Ruddle NH (1999) Lymphoid neo-organogenesis: lympho-toxin’s role in inflammation and development. Immunol Res 19:119–125. https://doi.org/10.1007/BF02786481
Hogg JC, Chu F, Utokaparch S et al (2004) The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 350:2645–2653. https://doi.org/10.1056/NEJMoa032158
Perros F, Dorfmüller P, Montani D et al (2012) Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 185:311–321. https://doi.org/10.1164/rccm.201105-0927OC
Marchal-Sommé J, Uzunhan Y, Marchand-Adam S et al (2006) Cutting edge: non-proliferating mature immune cells form a novel type of organized lymphoid structure in idiopathic pulmonary fibrosis. J Immunol 176:5735–5739. https://doi.org/10.4049/jimmunol.176.10.5735
Elliot JG, Jensen CM, Mutavdzic S et al (2004) Aggregation of lymphoid cells in the airways of nonsmokers, smokers and subjects with asthma. Am J Respir Crit Care Med 169:712–718. https://doi.org/10.1164/rccm.200308-1167C
Rangel-Moreno J, Harton L, Navarro C et al (2006) Inducible bronchus-associated lymphoid tissue (iBALT) in patients with pulmonary complications of rheumatoid arthritis. J Clin Invest 116:3183–3194. https://doi.org/10.1172/JCI28756
Dieu-Nosjean MC, Antoine M, Danel C et al (2008) Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol 26:4410–4417. https://doi.org/10.1200/JCO.2007.15.0284
Sautès-Fridman C, Lawand M, Giraldo NA et al (2016) Tertiary lymphoid structures in cancers: prognostic value, regulation, and manipulation for therapeutic intervention. Front Immunol 7:407. https://doi.org/10.3389/fimmu.2016.00407
Frija-Masson J, Martin C, Regard L et al (2017) Bacteria-driven peribronchial lymphoid neogenesis in bronchiectasis and cystic fibrosis. Eur Respir J 49(4). pii: 1601873. https://doi.org/10.1183/13993003.01873-2016
Vaincre la Mucoviscidose, INED. French cystic fibrosis registry. Annual data report 2015. http://www.vaincrelamuco.org/sites/default/files/french_cf_patient_registry_2015.pdf
Cystic Fibrosis Foundation 2016-Patient Registry-Annual data report. https://www.cff.org/Research/Researcher-Resources/Patient-Registry/2016-Patient-Registry-Reports/
Foo SY, Phipps S (2010) Regulation of inducible BALT formation and contribution to immunity and pathology. Mucosal Immunol 3:537–544. https://doi.org/10.1038/mi.2010.52
Crother TR, Ma J, Jupelli M et al (2012) Plasmacytoid dendritic cells play a role for effective innate immune responses during chlamydia pneumoniae infection in mice. PLoS One 7(10):e48655. https://doi.org/10.1371/journal.pone.0048655
Finkin S, Yuan D, Stein I et al (2015) Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat Immunol 16:1235–1244. https://doi.org/10.1038/ni.3290
Joshi NS, Akama-Garren EH, Lu Y et al (2015) Regulatory T cells in tumor-associated tertiary lymphoid structures suppress anti-tumor T cell responses. Immunity 43:579–590. https://doi.org/10.1016/j.immuni.2015.08.006
Martin C, Thevenot G, Danel S et al (2011) Pseudomonas aeruginosa induces vascularendothelial growth factor synthesis in airway epithelium in vitro and in vivo. Eur Resp J 38:939–946. https://doi.org/10.1183/09031936.00134910
Ius F, Sommer W, Tudorache I et al (2015) Preemptive treatment with therapeutic plasma exchange and rituximab for early donor-specific antibodies after lung transplantation. J Heart Lung Transplant 34:50–58. https://doi.org/10.1016/j.healun.2014.09.019
National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011) Guide for the care and use of laboratory animals, 8th ed. National Academies Press (US), Washington (DC). https://doi.org/10.17226/12910
The European Parliament and the Council of the European Union. 2010. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes. Off J Eur Communities L276:33–79
Nicklas W, Baneux P, Boot R et al (2002) Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab Anim 36:20–42. https://doi.org/10.1258/0023677021911740
Van Heeckeren AM, Schluchter MD (2002) Murine models of chronic Pseudomonas aeruginosa lung infection. Lab Anim 36:291–312. https://doi.org/10.1258/002367702320162405
Das S, MacDonald K, Chang HY, Mitzner W (2013) A simple method of mouse lung intubation. J Vis Exp 73:e50318. https://doi.org/10.3791/50318
Hsia CC, Hyde DM, Ochs M, Weibel ER, ATS/ERS Joint Task Force on Quantitative Assessment of Lung Structure (2010) An Official Research Policy Statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med 181:394–418. https://doi.org/10.1164/rccm.200809-1522ST
Palavecino EL (2014) Clinical, epidemiologic, and laboratory aspects of methicillin-resistant Staphylococcus aureus infections. Methods Mol Biol 1085:1–24. https://doi.org/10.1007/978-1-62703-664-1_1
Goerke C, Wolz C (2010) Adaptation of Staphylococcus aureus to the cystic fibrosis lung. Int J Med Microbiol 300:520–525. https://doi.org/10.1016/j.ijmm.2010.08.003
Teichgräber V, Ulrich M, Endlich N et al (2008) Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat Med 14:382–391
Morissette C, Skamene E, Gervais F (1995) Endobronchial inflammation following Pseudomonas aeruginosa infection in resistant and susceptible strains of mice. Infect Immun 63:1718–1724
Funding
This work was supported by a grant from Association Vaincre la Mucoviscidose (RF201605016 22/1/2/51), by INSERM, and by Paris Descartes and Sorbonne Universities.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Teillaud, JL., Regard, L., Martin, C., Sibéril, S., Burgel, PR. (2018). Exploring the Role of Tertiary Lymphoid Structures Using a Mouse Model of Bacteria-Infected Lungs. In: Dieu-Nosjean, MC. (eds) Tertiary Lymphoid Structures. Methods in Molecular Biology, vol 1845. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8709-2_13
Download citation
DOI: https://doi.org/10.1007/978-1-4939-8709-2_13
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-8708-5
Online ISBN: 978-1-4939-8709-2
eBook Packages: Springer Protocols