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(American Journal of Pathology. 2006;168:1169-1178.)
© 2006 American Society for Investigative Pathology

Kupffer Cell-Dependent Hepatitis Occurs during Influenza Infection

Noelle K. Polakos^*, Judith C. Cornejo, Debbie A. Murray^*, Kate O. Wright, John J. Treanor, I. Nicholas Crispe^*, David J. Topham^* and Robert H. Pierce

From the Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology/Aab Institute of Biomedical Sciences,^* the Department of Pathology and Laboratory Medicine, and the Department of Medicine Division of Infectious Diseases, University of Rochester Medical Center, Rochester, New York

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.

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