CCR2+TREM-1+ monocytes promote Natural killer T cell dysfunction contributing towards HBV disease progression

Abstract

Abstract Natural killer T (NKT) cells are amongst the most important innate immune cells against Hepatitis B virus (HBV) infection. Moreover, previous studies have shown that HBV infection induced TREM-1 + expression in monocyte and secretion of inflammatory cytokines. Thus, this prompted us to elucidate the role of TREM-1 + monocytes in regulating the function of NKT cells. Ninety patients and 20 healthy participants were enrolled in the study. The percentage and phenotype of iNKT cells and TREM-1 + monocytes were measured in the peripheral blood of healthy controls (HC), patients with chronic HBV infection (CHB), HBV-related liver cirrhosis (LC), and HBV-related acute-on-chronic liver failure (ACLF) via flow cytometry. Moreover, co-culture experiments with NKT cells and TREM-1 overexpressing THP-1 cells were performed to determine the role of TREM-1 in regulation of NKT cell function. We observed that the percentage of NKT cells and CD4-NKT cells gradually decreased, whereas percentage of CCR2 + TREM-1 + monocytes increased with the progression of the disease. In addition, activation of the TREM-1 signaling pathway induced the secretion of inflammatory cytokines leading to pyroptosis of NKT cells and secretion of IL-17 contributing towards disease progression. Therefore, this study suggests that blocking the activation of TREM-1 in monocytes could promote the elimination of HBV by inhibiting pyroptosis of NKT cells and restoring their function. However, further studies are required to validate these results that would help in developing new treatment strategies for patients with HBV infections.