Brucella-infected hepatocytes mediate potentially tissue-damaging immune responses

DELPINO MV,; BARRIONUEVO, P; SCIAN R; FOSSATI CA,; BALDI, PC

JOURNAL OF HEPATOLOGY

ELSEVIER SCIENCE BV

Lugar: AMSTERDAM; Año: 2010 vol. 53 p. 145 - 154

0168-8278

Background/Aims: Hepatic involvement is frequent in human brucellosis. While different histopathological lesions have been reported in these patients, the underlying cellular and molecular mechanisms have not been addressed. Methods: This study assessed whether Brucella abortus can infect a human hepatoma cell line and induce a proinflammatory response in these cells. Results: The bacterium not only infected the human hepatoma cell line HepG2 but also exhibited intracellular replication. The infection induced hepatoma cells to secrete IL-8, and supernatants from Brucella-infected hepatoma cells were shown to induce the migration of human neutrophils. The infection also induced the expression of the intercellular adhesion molecule ICAM-1 on hepatoma cells, and the adhesion of neutrophils to these cells was significantly higher than to uninfected hepatoma cells. ICAM-1 expression was also induced by stimulation of hepatoma cells with supernatants from Brucella-infected neutrophils. While Brucella infection did not induce the expression of matrix metalloproteinases (MMPs) in hepatoma cells, it induced significantly MMP-9 in neutrophils. Hepatoma cells apoptosis was induced significantly by B. abortus infection and also by stimulation with supernatants from Brucella-infected neutrophils. Conclusions: The present study provides clues regarding potential mechanisms of tissue damage during liver brucellosis.