Type I interferon receptor signaling delays Kupffer cell replenishment during acute fulminant viral hepatitis

Abstract

Viral infection can cause fulminant hepatitis, which in turn is a major cause of acute liver failure. Herein, we aimed to study the role of type 1 interferon responses in acute viral hepatitis. We identified that during infection with DNA-encoded viruses, type 1 interferon receptor triggering of blood monocytes delays the development of monocyte-derived Kupffer cells. This points to new therapeutic strategies for acute viral hepatitis.

Type-1 IFN primed monocytes in pathogenesis of idiopathic pulmonary fibrosis

“…Intriguingly, a murine study that showed type 1 IFN activation in infiltrating monocytes delayed their differentiation to macrophages in the liver during hepatitis C infection, although the mechanism for this was unclear (54).…”

Reply to: “Lack of Kupffer cell depletion in diethylnitrosamine-induced hepatic inflammation”

“…Recent studies demonstrated fulminant KC loss during viral or bacterial infection, as well as after toxic hepatic injury. [3][4][5][6] Furthermore, upon diphtheria toxin-induced KC depletion infiltrating monocytes can differentiate to monocyte-derived KCs (MoKCs). 7 Similarly, KCs that were depleted during virus-induced hepatitis and then replenished by F4/80 + -CLEC4F + MoKCs were indistinguishable from embryo-derived KCs, when analysed by cell surface receptor expression.…”

“…7 Similarly, KCs that were depleted during virus-induced hepatitis and then replenished by F4/80 + -CLEC4F + MoKCs were indistinguishable from embryo-derived KCs, when analysed by cell surface receptor expression. 3 Alazawi and Knolle speculated that transient KC loss could be generally associated with liver injury. 8 Indeed, the DEN model studied by Kessler et al is very different when compared with infection models.…”

“…This way myeloid cell function, including KC disappearance, might be directly and indirectly influenced by different cytokines. 3,[9][10][11][12][13] The liver is a complex and highly structured organ. Therefore, the anatomical site of inflammation might influence KC immunity.…”

Therapeutic spectrum of interferon‐β in ischemic stroke

“…IFNs have been recognized to be deeply implicated in the pathogenesis of several diseases, for example, collagen diseases such as rheumatoid arthritis (Conigliaro et al, ), systemic lupus erythematosus (SLE) (Gao, Anolik, & Looney, ), multiple sclerosis (Rudick & Goelz, ), insulin‐dependent diabetes mellitus (Qaisar, Jurczyk, & Wang, ), pancreatic cancer (Booy, Hofland, & van Eijck, ), fulminant hepatitis (Borst et al, ), atherosclerosis (Moss & Ramji, ), and allergic diseases (Gonzales‐van Horn & Farrar, ). IFNs are clinically used in the therapy against viral infections such as hepatitis B and C (Asselah & Marcellin, ; Jaeckel et al, ) and for different malignancies (Baron et al, ; Imanishi, ).…”