First Author | Kozik JH | Year | 2016 |
Journal | Sci Rep | Volume | 6 |
Pages | 28556 | PubMed ID | 27328755 |
Mgi Jnum | J:236023 | Mgi Id | MGI:5804477 |
Doi | 10.1038/srep28556 | Citation | Kozik JH, et al. (2016) Attenuated viral hepatitis in Trem1-/- mice is associated with reduced inflammatory activity of neutrophils. Sci Rep 6:28556 |
abstractText | TREM1 (Triggering Receptor Expressed on Myeloid Cells 1) is a pro-inflammatory receptor expressed by phagocytes, which can also be released as a soluble molecule (sTREM1). The roles of TREM1 and sTREM1 in liver infection and inflammation are not clear. Here we show that patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection manifest elevated serum levels of sTREM1. In mice, experimental viral hepatitis induced by infection with Lymphocytic Choriomeningitis Virus (LCMV)-WE was likewise associated with increased sTREM1 in serum and urine, and with increased TREM1 and its associated adapter molecule DAP12 in the liver. Trem1-/- mice showed accelerated clearance of LCMV-WE and manifested attenuated liver inflammation and injury. TREM1 expression in the liver of wild-type mice was mostly confined to infiltrating neutrophils, which responded to LCMV by secretion of CCL2 and TNF-alpha, and release of sTREM1. Accordingly, the production of CCL2 and TNF-alpha was decreased in the livers of LCMV-infected Trem1-/- mice, as compared to LCMV-infected wildtype mice. These findings indicate that TREM1 plays a role in viral hepatitis, in which it seems to aggravate the immunopathology associated with viral clearance, mainly by increasing the inflammatory activity of neutrophils. |