A Major Role for Myeloid-Derived Suppressor Cells and a Minor Role for Regulatory T Cells in Immunosuppression during Staphylococcus aureus Infection

作者：Tebartz Christina; Horst Sarah Anita; Sparwasser Tim; Huehn Jochen; Beineke Andreas; Peters Georg; Medina Eva^*

来源：The Journal of Immunology, 2015, 194(3): 1100-1111.

DOI：10.4049/jimmunol.1400196

Staphylococcus aureus can cause difficult-to-treat chronic infections. We recently reported that S. aureus chronic infection was associated with a profound inhibition of T cell responses. In this study, we investigated the mechanisms responsible for the suppression of T cell responses during chronic S. aureus infection. Using in vitro coculture systems, as well as in vivo adoptive transfer of CFSE-labeled OT-II cells, we demonstrated the presence of immunosuppressive mechanisms in splenocytes of S. aureus-infected mice that inhibited the response of OT-II cells to cognate antigenic stimulation. Immunosuppression was IL-10/TGF-beta independent but required cell-cell proximity. Using DEREG and Foxp3(gfp) mice, we demonstrated that CD4(+) CD25(+)Foxp3(+) regulatory T cells contributed, but only to a minor degree, to bystander immunosuppression. Neither regulatory B cells nor tolerogenic dendritic cells contributed to immunosuppression. Instead, we found a significant expansion of granulocytic (CD11b(+)Ly6G(+)Ly6C(low)) and monocytic (CD11b(+)Ly6G(-)Ly6C(high)) myeloid-derived suppressor cells (MDSC) in chronically infected mice, which exerted a strong immunosuppressive effect on T cell responses. Splenocytes of S. aureus-infected mice lost most of their suppressive activity after the in vivo depletion of MDSC by treatment with gemcitabine. Furthermore, a robust negative correlation was observed between the degree of T cell inhibition and the number of MDSC. An increase in the numbers of MDSC in S. aureus-infected mice by adoptive transfer caused a significant exacerbation of infection. In summary, our results indicate that expansion of MDSC and, to a minor degree, of regulatory T cells in S. aureus-infected mice may create an immunosuppressive environment that sustains chronic infection.

• 出版日期2015-2-1
• 单位河北医科大学