CD8α⁻ conventional dendritic cells control Vβ T‐cell immunity in response to Staphylococcus aureus infection in mice

Abstract

Dendritic cells (DCs) are potent immune cells that control innate and adaptive immune responses. Previous studies have shown that the DCs are required for protection against Staphylococcus aureus infection. However, the role of conventional DC (cDC) subsets during S. aureus infection in vivo has not been well investigated. In this study, we examined the function of spleen DC subsets in the activation of immunity against S. aureus infection. C57BL/6 mice were infected intravenously with S. aureus and DC and T‐cell activation were analyzed in vivo. We found that the spleen CD8α− cDCs phagocytosed S. aureus more efficiently than type‐1 conventional DCs (cDC1s) did. Moreover, the CD8α− cDCs contributed to the production of pro‐inflammatory cytokines in response to S. aureus infection, whereas the cDC1s did not. In addition, infection with S. aureus promoted an increase in the number of Vβ T cells. The CD4+ and CD8+ Vβ T cells up‐regulated the production of interferon‐γ (IFN‐γ) and interleukin‐17 (IL‐17) in response to S. aureus infection. Importantly, the induction of IFN‐γ and IL‐17 production in CD4+ and CD8+ Vβ T cells was mediated by S. aureus‐stimulated CD8α− cDCs, whereas cDC1s failed to promote IFN‐γ and IL‐17 production in the cells. Therefore, these data suggested that the spleen CD8α− cDCs are the main DC subsets for induction of S. aureus superantigen‐specific immunity.

Antigen specific activation of cytotoxic CD8+ T cells by Staphylococcus aureus infected dendritic cells

“…We observed that CD8 + T cells were not only activated through the recognition of their specific peptide at the surface of infected DCs but also in the absence of this peptide, albeit at lower levels. This is consistent with studies highlighting the role of superantigens, such as TSST-1, in the activation of T cells (Darisipudi et al, 2018;Balraadjsing et al, 2019;Zhang et al, 2020). Such an activation can also induce the anergy of T cells (O'Hehir and Lamb, 1990;Cornwell and Rogers, 2010), and therefore a failure of T cell response.…”

“…In vitro, only BDCA1 + myeloid DCs are able to engulf S. aureus and strongly upregulate the expression of costimulatory molecules and production of proinflammatory cytokines, inducing T cell differentiation into IFN-g-producing CD4 + and CD8 + T cells (Jin et al, 2014). The capacity of DCs to internalize S. aureus and their ensuing maturation is consistent with previous results obtained in vitro (Balraadjsing et al, 2019) or in vivo (Zhang et al, 2020). This maturation could partly be due to the activation of the TLR2-MyD88 pathway after the recognition of S. aureus lipoproteins as shown in vivo (Schmaler et al, 2011;Darisipudi et al, 2018).…”

“…DCs are involved in the recruitment of neutrophils, and the co-culture of S. aureusinfected BDCA1 + DCs with T cells induces the proliferation of T cells and their production of IFN-g (Jin et al, 2014). In a murine model, Zhang et al demonstrated that after infection, the conventional DCs CD8aare the main producers of proinflammatory cytokines and activators of adaptive cells (Zhang et al, 2020). Plasmacytoid DCs are likewise involved in the immune response against S. aureus (Parcina et al, 2008;Parcina et al, 2013).…”