Brucella-infected hepatocytes mediate potentially tissue-damaging immune responses

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 significantly induced MMP-9 in neutrophils. Hepatoma cell apoptosis was significantly induced 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. 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. This study assessed whether Brucella abortus can infect a human hepatoma cell line and induce a proinflammatory response in these cells. 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 significantly induced MMP-9 in neutrophils. Hepatoma cell apoptosis was significantly induced by B. abortus infection and also by stimulation with supernatants from Brucella-infected neutrophils. The present study provides clues regarding potential mechanisms of tissue damage during liver brucellosis.