Immunological gap in the infectious animal model for biliary atresia.
BACKGROUND
Extrahepatic biliary atresia (EHBA), the etiology of which still remains unclear, occurs exclusively in newborns and has recently been simulated in an animal model. It is possible to trigger an EHBA corresponding to the human disease by means of intraperitoneal infection of newborn Balb/c mice with rhesus rotavirus (RRV). The aim of the present study was to determine the conditions and circumstances for inducing biliary atresia in this model focusing on first-line immunological aspects.


METHODS
Newborn as well as pregnant Balb/c mice were intraperitoneally infected with RRV.


RESULTS
The highest incidence of cholestasis (86%) was achieved by infection with 10(6) PFU/ml RRV within the first 12 h postpartum, resulting in EHBA with a lethality of 100%. However, the later the newborn mouse is infected, the less likelihood there is that EHBA is triggered. Additionally, the incidence of biliary atresia in this model depends on the quantity of the virus that is given intraperitoneally. However, the development of biliary atresia is not correlated to the virus in the liver. The antepartum infection of pregnant mice does not induce EHBA in the offspring. Female mice that are immunized against RRV protect their newborns from developing RRV-induced cholestasis and EHBA. This protection is transmitted transplacentally and not by breast milk.


CONCLUSIONS
It is obvious that a temporary immunological gap is essential for virally induced EHBA. Further studies should focus on specific parameters of the immune system of newborn mice in this biliary atresia model.
Czech-Schmidt
G
G
Department of Pediatric Surgery, Medical School Hannover, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany.
Verhagen
W
W
Szavay
P
P
Leonhardt
J
J
Petersen
C
C
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001656:Biliary Atresia / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D002779:Cholestasis / Q000821:virology; D005260:Female; D007109:Immunity; D007114:Immunization; D015994:Incidence; D008431:Maternal-Fetal Exchange; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D010532:Peritoneal Diseases / Q000150:complications* / Q000209:etiology / Q000517:prevention & control; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D012400:Rotavirus Infections / Q000150:complications* / Q000209:etiology / Q000517:prevention & control