期刊
MOLECULAR IMMUNOLOGY
卷 94, 期 -, 页码 107-120出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2017.10.009
关键词
Interferon gamma; Myeloid derived suppressor cells; Tuberculosis; Programmed death 1/programmed death 1 ligands
资金
- National Natural Science Foundation of China [31470877, 81261160323]
- National Key Research and Development Program of China [2016YFC1200105]
- National Science and Technology Key Projects for Major Infectious Diseases [2017ZX10302301, 2013ZX10003001]
- Science and Technology Planning Project of Guangzhou [201704020226, 2016A020050001, 201604020006]
- Guangdong Natural Science Foundation [2015A030311009]
- Guangdong Natural Science Found for Distinguished Young Scholars [2016A030306004]
- Guangdong Special Support Program for Youth Science and Technology Innovation Talents [2015TQ01R473]
- Guangdong Peal River New Star Program [201610010064]
- 111 Project [B13037]
Myeloid-derived suppressor cells (MDSCs) have recently been described to inhibit protective T-cell responses in tuberculosis (TB). T cells play an important role in the immunity to Mycobacterium tuberculosis, and are the major producers of IFN-gamma. However, the impact of IFN-gamma on MDSCs during TB is still not completely understood. Our study demonstrated a significant correlation between MDSC levels and TB progression, suggesting that MDSCs may serve as a potential marker in diagnosis or treatment of TB. Culture with GM-csf and IL-6 promoted peripheral blood mononuclear cells (PBMCs) to differentiate into functional CD33(+)FILA-DRlow MDSC-like cells. Moreover, we report for the first time, that IFN-gamma-educated CD33(+)HLA-DRlow MDSCs have less suppressive potential to diminish T-cell responses, including IFN-gamma production. Further investigations revealed that suppressive function of CD33(+)HIA-DRlow MDSCs was dependent on programmed death-1/programmed death-1 ligand-2 (PD1/PD-L2) pathway and required direct cell cell contact. IFN-gamma dampened the immuno-suppressive activity of CD33(+)HLA-DRlow MDSCs by inhibiting PD-1/PD-L2 pathway, indicating the existence of a negative feedback loop between IFN-gamma and functional MDSC expansion. In summary, our study revealed a novel mechanism by which IFN-gamma decreases the suppressive function of MDSCs, suggesting that antagonizing suppressive functions of MDSCs by IFN-gamma could enhance immune responses against TB infection.
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