Abstract
Background Tertiary lymphoid structures (TLS) are triggered by persistent bronchopulmonary infection with Staphylococcus aureus, but their roles remain elusive. The present study sought to examine the effects of B- and/or T-cell depletion on S. aureus infection and TLS development (lymphoid neogenesis) in mice.
Methods C57Bl/6 mice were pre-treated with 1) an anti-CD20 monoclonal antibody (mAb) (B-cell depletion) or 2) an anti-CD4 and/or an anti-CD8 mAb (T-cell depletion) or 3) a combination of anti-CD20, anti-CD4 and anti-CD8 mAbs (combined B- and T-cell depletion) or 4) isotype control mAbs. After lymphocyte depletion, mice were infected by intratracheal instillation of agarose beads containing S. aureus (106 CFU per mouse). 14 days later, bacterial load and lung inflammatory cell infiltration were assessed by cultures and immunohistochemistry, respectively.
Results 14 days after S. aureus-bead instillation, lung bacterial load was comparable between control and lymphocyte-depleted mice. While TLS were observed in the lungs of infected mice pre-treated with control mAbs, these structures were disorganised or abolished in the lungs of lymphocyte-depleted mice. The absence of CD20+ B-lymphocytes had no effect on CD3+ T-lymphocyte infiltration, whereas CD4+/CD8+ T-cell depletion markedly reduced CD20+ B-cell infiltration. Depletion of CD4+ or CD8+ T-cells separately had limited effect on B-cell infiltration, but led to the absence of germinal centres.
Conclusion TLS disorganisation is not associated with loss of infection control in mice persistently infected with S. aureus.
Abstract
Disorganisation of peribronchial lymphoid follicles did not result in increased bacterial load nor in decreased survival in a mouse model of persistent lung infection. Lymphoid follicles may not be essential for controlling lung bacterial infection. https://bit.ly/3lOgNEG
Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.04352-2020
This article has supplementary material available from erj.ersjournals.com
Conflict of interest: L. Regard has nothing to disclose.
Conflict of interest: C. Martin reports personal fees from Zambon, outside the submitted work.
Conflict of interest: J-L. Teillaud has nothing to disclose.
Conflict of interest: H. Lafoeste has nothing to disclose.
Conflict of interest: H. Vicaire has nothing to disclose.
Conflict of interest: M.Z. Ladjemi has nothing to disclose.
Conflict of interest: E. Ollame-Omvane has nothing to disclose.
Conflict of interest: S. Sibéril has nothing to disclose.
Conflict of interest: P-R. Burgel reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, Pfizer, Vertex, Zambon and Insmed, outside the submitted work.
Support statement: This work was funded by Vaincre la Mucoviscidose and La Fondation du Souffle/Fonds de Recherche en Santé Respiratoire and by Legs Pascal Bonnet. Funding sources were not involved in the study design; the collection, analysis and interpretation of the data; the writing of the report and the decision to submit the article for publication. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received March 19, 2020.
- Accepted October 11, 2020.
- Copyright ©ERS 2021