Kupffer cell-dependent hepatitis occurs during influenza infection.
Respiratory infections, including influenza in humans, are often accompanied by a hepatitis that is usually mild and self-limiting. The mechanism of this kind of liver damage is not well understood. In the present study, we show that influenza-associated hepatitis occurs due to the formation of inflammatory foci that include apoptotic hepatocytes, antigen-specific CD8(+) T cells, and Kupffer cells. Serum aminotransaminase levels were elevated, and both the histological and serum enzyme markers of hepatitis were increased in secondary influenza infection, consistent with a primary role for antigen-specific T cells in the pathogenesis. No virus could be detected in the liver, making this a pure example of "collateral damage" of the liver. Notably, removal of the Kupffer cells prevented the hepatitis. Such hepatic collateral damage may be a general consequence of expanding CD8(+) T-cell populations during many extrahepatic viral infections, yielding important implications for liver pathobiology.
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Box 626, Rochester, NY 14642-8609, USA.
Noelle K
NK
Polakos
Judith C
JC
Cornejo
Debbie A
DA
Murray
Kate O
KO
Wright
John J
JJ
Treanor
I Nicholas
IN
Crispe
David J
DJ
Topham
Robert H
RH
Pierce
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006505:Hepatitis / Q000209:etiology* / Q000473:pathology / Q000821:virology; D022781:Hepatocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000150:complications* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D007728:Kupffer Cells / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged
D000410:Alanine Transaminase