title: Farnesoid X Receptor in Mice Prevents Severe Liver Immunopathology During Lymphocytic Choriomeningitis Virus Infection.
abstract: BACKGROUND
  Bile acids (BAs) are steroid molecules that are synthesized in the liver. In addition to their important role as a surfactant in solubilizing lipids and promoting the absorption of lipids in the gastrointestinal tract, they act as inflammagens. The role of BAs and their receptor farnesoid X receptor (FXR) during viral infection has not been studied in detail.
  
  
  METHODS
  By using FXR-deficient mice, we investigated the role of bile acid receptor FXR during infection with lymphocytic choriomeningitis virus (LCMV). The importance of FXR in inducing IFN-I and monocytes proliferation were investigated and viral titers and T cell exhaustion were analyzed at different time points.
  
  
  RESULTS
  This study shows that controlled levels of BAs activate FXR in hepatocytes and FXR in response upregulates the production of type I interferon. In turn, FXR maintains BAs within a balanced range to inhibit their toxic effects. The absence of FXR results in high levels of BAs, which inhibit the proliferation of monocytes and result in a defect in viral elimination, consequently leading to T cell exhaustion.
  
  
  CONCLUSIONS
  We found that FXR contributes to IFN-I production in hepatocytes and balances BA levels to inhibit their toxic effects on monocytes.
authors.forename: Nadine
authors.initials: N
authors.lastname: Honke
authors.forename: Namir
authors.initials: N
authors.lastname: Shaabani
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hardt
authors.forename: Caroline
authors.initials: C
authors.lastname: Krings
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
authors.forename: Verena
authors.initials: V
authors.lastname: Keitel
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D008216:Lymphocytic Choriomeningitis / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014779:Virus Replication; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D007370:Interferon Type I; D007555:Isoxazoles; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C412815:GW 4064
keywords: Bile acids; FXR; IFN-I; LCMV; Monocytes; NR1H4