Effective control of<i>Staphylococcus aureus</i>lung infection despite tertiary lymphoid structure disorganisation

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 (10 6 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 .