Exploring the Role of Tertiary Lymphoid Structures Using a Mouse Model of Bacteria-Infected Lungs

Overview

Journal Methods Mol Biol

Specialty Molecular Biology

Date 2024 Nov 11

PMID 39527228

Authors

Jean-Luc Teillaud

Lucile Regard

Clemence Martin

Sophie Siberil

Pierre-Regis Burgel

Affiliations

Soon will be listed here.

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 the 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.

References

Bienenstock J, Johnston N, PEREY D . Bronchial lymphoid tissue. I. Morphologic characteristics. Lab Invest. 1973; 28(6):686-92. View

Bienenstock J, Johnston N, PEREY D . Bronchial lymphoid tissue. II. Functional characterisitics. Lab Invest. 1973; 28(6):693-8. View

Pabst R, Gehrke I . Is the bronchus-associated lymphoid tissue (BALT) an integral structure of the lung in normal mammals, including humans?. Am J Respir Cell Mol Biol. 1990; 3(2):131-5. DOI: 10.1165/ajrcmb/3.2.131. View

Ruddle N . Lymphoid neo-organogenesis: lymphotoxin's role in inflammation and development. Immunol Res. 1999; 19(2-3):119-25. DOI: 10.1007/BF02786481. View

Hogg J, Chu F, Utokaparch S, Woods R, Elliott W, Buzatu L . The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004; 350(26):2645-53. DOI: 10.1056/NEJMoa032158. View

Perros F, Dorfmuller P, Montani D, Hammad H, Waelput W, Girerd B . Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2011; 185(3):311-21. DOI: 10.1164/rccm.201105-0927OC. View

Marchal-Somme J, Uzunhan Y, Marchand-Adam S, Valeyre D, Soumelis V, Crestani B . Cutting edge: nonproliferating mature immune cells form a novel type of organized lymphoid structure in idiopathic pulmonary fibrosis. J Immunol. 2006; 176(10):5735-9. DOI: 10.4049/jimmunol.176.10.5735. View

Elliot J, Jensen C, Mutavdzic S, Lamb J, Carroll N, James A . Aggregations of lymphoid cells in the airways of nonsmokers, smokers, and subjects with asthma. Am J Respir Crit Care Med. 2004; 169(6):712-8. DOI: 10.1164/rccm.200308-1167OC. View

Rangel-Moreno J, Hartson L, Navarro C, Gaxiola M, Selman M, Randall T . Inducible bronchus-associated lymphoid tissue (iBALT) in patients with pulmonary complications of rheumatoid arthritis. J Clin Invest. 2006; 116(12):3183-94. PMC: 1678820. DOI: 10.1172/JCI28756. View

10.

Dieu-Nosjean M, Antoine M, Danel C, Heudes D, Wislez M, Poulot V . Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol. 2008; 26(27):4410-7. DOI: 10.1200/JCO.2007.15.0284. View

11.

Domblides C, Rochefort J, Riffard C, Panouillot M, Lescaille G, Teillaud J . Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation. Front Immunol. 2021; 12:698604. PMC: 8279885. DOI: 10.3389/fimmu.2021.698604. View

12.

Helmink B, Reddy S, Gao J, Zhang S, Basar R, Thakur R . B cells and tertiary lymphoid structures promote immunotherapy response. Nature. 2020; 577(7791):549-555. PMC: 8762581. DOI: 10.1038/s41586-019-1922-8. View

13.

Petitprez F, De Reynies A, Keung E, Chen T, Sun C, Calderaro J . B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020; 577(7791):556-560. DOI: 10.1038/s41586-019-1906-8. View

14.

Cabrita R, Lauss M, Sanna A, Donia M, Skaarup Larsen M, Mitra S . Tertiary lymphoid structures improve immunotherapy and survival in melanoma. Nature. 2020; 577(7791):561-565. DOI: 10.1038/s41586-019-1914-8. View

15.

Nichols D, Morgan S, Skalland M, Vo A, Van Dalfsen J, Singh S . Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist. J Clin Invest. 2023; 133(10). PMC: 10178839. DOI: 10.1172/JCI167957. View

16.

Foo S, Phipps S . Regulation of inducible BALT formation and contribution to immunity and pathology. Mucosal Immunol. 2010; 3(6):537-44. DOI: 10.1038/mi.2010.52. View

17.

Crother T, Ma J, Jupelli M, Chiba N, Chen S, Slepenkin A . Plasmacytoid dendritic cells play a role for effective innate immune responses during Chlamydia pneumoniae infection in mice. PLoS One. 2012; 7(10):e48655. PMC: 3485374. DOI: 10.1371/journal.pone.0048655. View

18.

Finkin S, Yuan D, Stein I, Taniguchi K, Weber A, Unger K . Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat Immunol. 2015; 16(12):1235-44. PMC: 4653079. DOI: 10.1038/ni.3290. View

19.

Joshi N, Akama-Garren E, Lu Y, Lee D, Chang G, Li A . Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses. Immunity. 2015; 43(3):579-90. PMC: 4826619. DOI: 10.1016/j.immuni.2015.08.006. View

20.

Devi-Marulkar P, Fastenackels S, Karapentiantz P, Goc J, Germain C, Kaplon H . Regulatory T cells infiltrate the tumor-induced tertiary lymphoïd structures and are associated with poor clinical outcome in NSCLC. Commun Biol. 2022; 5(1):1416. PMC: 9789959. DOI: 10.1038/s42003-022-04356-y. View