Brucella-infected hepatocytes mediate potentially tissue-damaging immune responses

DELPINO M. VICTORIA; BARRIONUEVO PAULA; SCIAN ROMINA; FOSSATI CARLOS A; BALDI PABLO C

JOURNAL OF HEPATOLOGY

ELSEVIER SCIENCE BV

Año: 2010 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 hepatocytes 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 hepatocytes to secrete IL-8, and supernatants from Brucella-infected hepatocytes were shown to induce the migration of human neutrophils. The infection also induced the expression of the intercellular adhesion molecule ICAM-1 on hepatocytes, and the adhesion of neutrophils to these cells was significantly higher than to uninfected hepatocytes. ICAM-1 expression was also induced by stimulation of hepatocytes with supernatants from Brucella-infected neutrophils. While Brucella infection did not induce the expression of matrix metalloproteinases (MMPs) in hepatocytes, it induced significantly MMP-9 in neutrophils. Hepatocyte 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. > Ms. Ref. No.:  JHEPAT-D-09-00418 > Title: Brucella-infected hepatocytes mediate potentially tissue-damaging > immune responses > Journal of Hepatology > > Dear Dr. Baldi, > > We are pleased to inform you that your paper "Brucella-infected > hepatocytes mediate potentially tissue-damaging immune responses" has been > accepted for publication in the Journal of Hepatology. However, before we > proceed with the publication of your paper, the editorial team has > requested that a few minor revisions be made to your manuscript.  Please > find below comments from the editorial team to guide you with your > revisions. > > Once you have completed your revisions, we kindly ask you to resubmit your > manuscript via the Elsevier Editorial System > (http://ees.elsevier.com/jhepat/). > > Your login details are as follows: > > Your username is: > Your password is: > > We would like to thank you for contributing this interesting paper to the > Journal of Hepatology and we look forward to receiving your revised > manuscript. > > Yours sincerely, > > Ira M. Jacobson > Associate Editor > > Peter R. Galle > Co-Editor > > Didier Samuel > Editor-In-Chief > Journal of Hepatology > Ms. Ref. No.:  JHEPAT-D-09-00418 > Title: Brucella-infected hepatocytes mediate potentially tissue-damaging > immune responses > Journal of Hepatology > > Dear Dr. Baldi, > > We are pleased to inform you that your paper "Brucella-infected > hepatocytes mediate potentially tissue-damaging immune responses" has been > accepted for publication in the Journal of Hepatology. However, before we > proceed with the publication of your paper, the editorial team has > requested that a few minor revisions be made to your manuscript.  Please > find below comments from the editorial team to guide you with your > revisions. > > Once you have completed your revisions, we kindly ask you to resubmit your > manuscript via the Elsevier Editorial System > (http://ees.elsevier.com/jhepat/). > > Your login details are as follows: > > Your username is: > Your password is: > > We would like to thank you for contributing this interesting paper to the > Journal of Hepatology and we look forward to receiving your revised > manuscript. > > Yours sincerely, > > Ira M. Jacobson > Associate Editor > > Peter R. Galle > Co-Editor > > Didier Samuel