A major role for myeloid-derived suppressor cells and a minor role for regulatory T cells in immunosuppression during Staphylococcus aureus infection

Christina Tebartz, Sarah Anita Horst, Tim Sparwasser, Jochen Huehn, Andreas Beineke, Georg Peters, Eva Medina

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65 Citations (Scopus)

Abstract

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-β independent but required cell-cell proximity. Using DEREG and Foxp3gfp 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+Ly6Clow) and monocytic (CD11b+Ly6G-Ly6Chigh) 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.

Original languageEnglish
Pages (from-to)1100-1111
Number of pages12
JournalJournal of Immunology
Volume194
Issue number3
DOIs
Publication statusPublished - 1 Feb 2015
Externally publishedYes

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