A Major Role for Myeloid-Derived Suppressor Cells and a Minor Role for Regulatory T Cells in Immunosuppression during Staphylococcus aureus Infection
| Autor: | Andreas Beineke, Georg Peters, Eva Medina, Christina Tebartz, Sarah A. Horst, Jochen Huehn, Tim Sparwasser |
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| Rok vydání: | 2015 |
| Předmět: |
Staphylococcus aureus
Adoptive cell transfer medicine.medical_treatment Regulatory B cells T cell Immunology Mice Transgenic Cell Communication Biology Severity of Illness Index T-Lymphocytes Regulatory Immunophenotyping Immune tolerance Immunomodulation Mice T-Lymphocyte Subsets Immune Tolerance medicine Animals Immunology and Allergy Myeloid Cells IL-2 receptor B-Lymphocytes Regulatory FOXP3 Immunosuppression Dendritic Cells Staphylococcal Infections Adoptive Transfer Coculture Techniques Disease Models Animal Phenotype medicine.anatomical_structure Myeloid-derived Suppressor Cell Cytokines Female Spleen |
| Zdroj: | The Journal of Immunology. 194:1100-1111 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1400196 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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