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.
Polakos
Noelle K
NK
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Box 626, Rochester, NY 14642-8609, USA.
Cornejo
Judith C
JC
Murray
Debbie A
DA
Wright
Kate O
KO
Treanor
John J
JJ
Crispe
I Nicholas
IN
Topham
David J
DJ
Pierce
Robert H
RH
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