Persistent accumulation of circulating monocytic myeloid-derived suppressor cells contributes to post-infectious immunosuppression in renal transplant recipients with bacterial infection: A pilot study

Introduction: Post-infectious immunosuppression is disadvantageous to patients' long-term outcomes, especially in transplant recipients receiving large doses of immunosuppressants. A growing body of evidence indicates the immunoregulatory ability of myeloid-derived suppressor cells (MDSCs). We herein investigate the characteristics of monocytic-MDSCs (M-MDSCs) in a cohort of renal transplant recipients with/without infection to clarify the potential involvement in post-infectious immunosuppression. Methods: The study prospectively included 28 adult recipients who underwent allogeneic ABO-compatible renal transplant. Blood samples were drawn at day 0, 7, 14, 28, 60 and 90 postoperation. The incidence of infection and treatment strategies were recorded. The frequency and absolute number of peripheral blood M-MDSCs as well as other immune cells were determined by flow cytometry. Immnosuppressive functions of M-MDSCs were analyzed by inhibition of T cells proliferation. mRNA levels of immunosuppressive molecules in sorted M-MDSCs were also examined. Results: 7 recipients were diagnosed with bacterial (n = 5) or viral (n = 2) infection and 3/5 of bacterial-infected recipients suffered from secondary infection during further follow-up. In the non-infected group, M-MDSCs numbers increased transiently during the early postoperative period, however, bacterial but not viral infection led to significant and persistent accumulation of M-MDSCs that remained at high levels after anti-infective treatments. M-MDSCs from infected recipients demonstrated potent ability to suppress T cells proliferation in vitro and negatively correlated with lymphocytes in vivo, yet not in the non-infected group. Inducible nitric oxide synthase (iNOS) mRNA levels were higher in sorted M-MDSCs when compared with monocytes, and suppressive activity was reversed by addition of a NOS inhibitor. Conclusions: Circulating M-MDSCs underwent significant and persistent increases after bacterial infection in renal transplant recipients, contributing to post-infectious immunodeficiency. Therefore, special attention should be given to M-MDSCs during the monitoring of immune status and infection management.