title: Attenuated viral hepatitis in Trem1-/- mice is associated with reduced inflammatory activity of neutrophils.
abstract: 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-α, and release of sTREM1. Accordingly, the production of CCL2 and TNF-α 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.
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Department of Medicine I, 20246 Hamburg, Germany.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Kozik
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Department of Medicine I, 20246 Hamburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Trautmann
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Department of Medicine I, 20246 Hamburg, Germany.
authors.forename: Antonella
authors.initials: A
authors.lastname: Carambia
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Department of Medicine I, 20246 Hamburg, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Preti
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Institute of Medical Microbiology, Virology and Hygiene, 20246 Hamburg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Lütgehetmann
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Institute of Pathology, 20246 Hamburg, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Krech
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Department of Medicine I, 20246 Hamburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Wiegard
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Institute of Biochemistry and Molecular Cell Biology, 20246 Hamburg, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Heeren
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Department of Medicine I, 20246 Hamburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Herkel
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000096:biosynthesis; D005260:Female; D006509:Hepatitis B / Q000097:blood / Q000276:immunology; D006526:Hepatitis C / Q000097:blood / Q000276:immunology; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1 / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D055815:Young Adult
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C408842:TREM1 protein, human; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha