Pam2 lipopeptides enhance the immunosuppressive activity of monocytic myeloid-derived suppressor cells by STAT3 signal in chronic inflammation

Abstract

Chronic inflammation develops when the immune system is unable to clear a persistent insult. Unresolved chronic inflammation leads to immunosuppression to maintain the internal homeostatic conditions, which is mediated primarily by myeloid-derived suppressor cells (MDSCs). Toll-like receptors 2 (TLR2) has an important role in chronic inflammation and can be activated by a vast number and diversity of TLR2 ligands, for example Pam 2 CSK4. However, the regulatory effect of TLR2 signaling on MDSCs in chronic inflammation remains controversial. This study demonstrated that heat-killed Mycobacterium bovis BCG-induced pathology-free chronic inflammation triggered suppressive monocytic MDSCs (M-MDSCs) that expressed TLR2. Activation of TLR2 signaling by Pam 2 CSK4 treatment enhanced immunosuppression of M-MDSCs by upregulating inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production partly through signal transducer and activator of transcription 3 (STAT3) activation. Thus, TLR2 has a fundamental role in promoting the MDSC-mediated immunosuppressive environment during chronic inflammation and might represent a potentially therapeutic target in chronic inflammation disease.

Keywords

• toll-like receptor 2 (tlr2)
• myeloid-derived suppressor cells (mdscs)
• monocytic mdscs (m-mdscs)
• signal transducer and activator of transcription 3 (stat3)
• inducible no synthase (inos/nos2)
• nitric oxide (no)
• chronic inflammation.