摘要
AIM: To develop an animal model of liver infection with Chlamydia pneumoniae (C. pneumoniae) in intraperito-neally infected mice for studying the presence of chlamy-diae 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 isola-tion in LLC-MK2 cells and fluorescence in situ hybridiza-tion (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 homoge-nates 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 sepa-rated 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. Stimula-tion of Kupffer cells by alive C. pneumoniae elicited high TNF-α levels. CONCLUSION: A productive infection by C. pneumo-niae 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 local-ized in the liver. One could speculate that C. pneumoniaeinfection, involving cells of the innate immunity such as Kupffer cells, could also trigger pathological immune re-actions involving the liver, as observed in human patients with primary biliary cirrhosis.
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 enzymelinked 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.
基金
Supported by MIUR, PRIN 2003 and 2005 to RC
关键词
衣原体
肝疾病
病理
治疗
临床
Chlamydia pneumoniae
Liver infection
Kupffer cells
Hepatocytes
Culture-isolation
Fluorescence in situ hybridization
TNF-α
Primary biliary cirrhosis
