Abstract
Background Tertiary lymphoid structures (TLS) are triggered by persistent bronchopulmonary infection with S. 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 pretreated with (1) an anti-CD20 mAb (B cell depletion) or (2) an anti-CD4 and/or an anti-CD8 mAbs (T cell depletion) or (3) a combination of anti-CD20, anti-CD4 and anti-CD8 mAbs (combined B and T cell depletion) or (4) with isotype control mAbs. After lymphocyte depletion, mice were infected by intratracheal instillation of agarose beads containing S. aureus (106 CFU/mouse). Fourteen days later, bacterial load and lung inflammatory cell infiltration were assessed by cultures and immunohistochemistry, respectively.
Results Fourteen 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 pretreated 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 lead to the absence of germinal center.
Conclusion TLS disorganisation is not associated with loss of infection control in mice persistently infected with S. aureus.
Footnotes
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Conflict of interest: Dr. Yan reports grants from National Institutes of Health, during the conduct of the study;.
Conflict of interest: Dr. Regard has nothing to disclose.
Conflict of interest: Dr. Martin reports personal fees from Zambon, outside the submitted work;.
Conflict of interest: Dr. Teillaud has nothing to disclose.
Conflict of interest: Dr. Lafoeste has nothing to disclose.
Conflict of interest: Dr. Vicaire has nothing to disclose.
Conflict of interest: Dr. Ladjemi has nothing to disclose.
Conflict of interest: Dr. Ollame-Omvane has nothing to disclose.
Conflict of interest: Dr. Sibéril has nothing to disclose.
Conflict of interest: Dr. Burgel reports personal fees from Astra-Zeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from Novartis, personal fees from Pfizer, personal fees from Vertex, personal fees from Zambon, personal fees from Insmed, outside the submitted work; .
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- Received March 19, 2020.
- Accepted October 11, 2020.
- Copyright ©ERS 2020