Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 28, 2006; 12(40): 6453-6457
Published online Oct 28, 2006. doi: 10.3748/wjg.v12.i40.6453
Chlamydia pneumoniae replicates in Kupffer cells in mouse model of liver infection
Antonella Marangoni, Manuela Donati, Francesca Cavrini, Rita Aldini, Silvia Accardo, Vittorio Sambri, Marco Montagnani, Roberto Cevenini
Antonella Marangoni, Manuela Donati, Francesca Cavrini, Silvia Accardo, Vittorio Sambri, Roberto Cevenini, Sezione di Microbiologia DMCSS, University of Bologna, Bologna, Italy
Rita Aldini, Dipartimento SMETC, University of Bologna, Bologna, Italy
Marco Montagnani, Dipartimento di Medicina Interna e Gastroenterologia, University of Bologna, Bologna, Italy
Supported by MIUR, PRIN 2003 and 2005 to RC
Correspondence to: Roberto Cevenini, MD, Sezione di Microbiologia DMCSS, University of Bologna, Policlinico S.Orsola, 9 Via Massarenti, Bologna 40138, Italy. roberto.cevenini@unibo.it
Telephone: +39-51-341632 Fax: +39-51-307397
Received: July 30, 2006
Revised: August 22, 2006
Accepted: September 18, 2006
Published online: October 28, 2006
Abstract

AIM: To develop an animal model of liver infection with Chlamydia pneumoniae (C. pneumoniae) in intraperitoneally infected mice for studying the presence of chlamydiae in Kupffer cells and hepatocytes.

METHODS: A total of 80 BALB/c mice were inoculated intraperitoneally with C. pneumoniae and sacrificed at various time points after infection. Chlamydiae were looked for in liver homogenates as well as in Kupffer cells and hepatocytes separated by liver perfusion with collagenase. C. pneumoniae was detected by both isolation in LLC-MK2 cells and fluorescence in situ hybridization (FISH). The releasing of TNFA-α by C. pneumoniae in vitro stimulated Kupffer cells was studied by enzyme-linked immunosorbent assay.

RESULTS: C. pneumoniae isolation from liver homogenates reached a plateau on d 7 after infection when 6 of 10 animals were positive, then decreased, and became negative by d 20. C. pneumoniae isolation from separated Kupffer cells reached a plateau on d 7 when 5 of 10 animals were positive, and became negative by d 20. The detection of C. pneumoniae in separated Kupffer cells by FISH, confirmed the results obtained by culture. Isolated hepatocytes were always negative. Stimulation of Kupffer cells by alive C. pneumoniae elicited high TNF-α levels.

CONCLUSION: A productive infection by C. pneumoniae may take place in Kupffer cells and C. pneumoniae induces a local pro-inflammatory activity. C. pneumoniae is therefore, able to act as antigenic stimulus when localized in the liver. One could speculate that C. pneumoniae infection, involving cells of the innate immunity such as Kupffer cells, could also trigger pathological immune reactions involving the liver, as observed in human patients with primary biliary cirrhosis.

Keywords: Chlamydia pneumoniae; Liver infection; Kupffer cells; Hepatocytes; Culture-isolation; Fluorescence in situ hybridization; TNF-α; Primary biliary cirrhosis