Differential roles of B and CD4/CD8 T cells in S. aureus-driven lung lymphoid neogenesis

Abstract

Introduction: Tertiary lymphoid structures (TLS) are triggered by persistent bronchopulmonary infection with Staphylococcus aureus (SA) in mice in 14 days. Here, we examined the effects of B and/or T-cell depletion on TLS development (lymphoid neogenesis) and bacterial infection 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 (Controls). After lymphocyte depletion, mice were infected by intratracheal instillation of agarose beads containing SA (105 CFU/mouse). Fourteen days later, bacterial load and lung inflammatory cell infiltration were assessed by cultures of lung homogenates and immunohistochemistry, respectively. Results: 14 days after SA-bead instillation, lung bacterial load was comparable between Control and lymphocyte depleted mice. While TLS were observed in the lungs of persistently SA-infected mice pretreated with control mAbs, these structures were disrupted in the lungs of depleted mice. The absence of CD20+ B-lymphocytes had no effect on CD3+ T-lymphocyte recruitment, whereas CD4+/CD8+ T-cell depletion markedly reduced CD20+ B-cell recruitment triggered by SA infection. Depletion of CD4+ or CD8+ T-cells separately lead to germinal centre disruption but had only limited effect on B-cell recruitment. Conclusion: TLS disruption is not associated with increased lung bacterial load in mice persistently infected with S. aureus. CD4+ and CD8+ T-cell are required for B-cell recruitment and germinal centre formation in response to persistent infection.