Chlamydia pneumoniae replicates in Kupffer cells in mouse model of liver infection.
OBJECTIVE
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-alpha 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-alpha levels.


CONCLUSIONS
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.
Marangoni
Antonella
A
Sezione di Microbiologia DMCSS, University of Bologna, Policlinico S.Orsola, 9 Via Massarenti, Bologna 40138, Italy.
Donati
Manuela
M
Cavrini
Francesca
F
Aldini
Rita
R
Accardo
Silvia
S
Sambri
Vittorio
V
Montagnani
Marco
M
Cevenini
Roberto
R
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000276:immunology / Q000473:pathology*; D016993:Chlamydophila pneumoniae / Q000254:growth & development* / Q000276:immunology / Q000472:pathogenicity; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007249:Inflammation; D007728:Kupffer Cells / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D008107:Liver Diseases / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000942:Antigens, Bacterial; D014409:Tumor Necrosis Factor-alpha