Toll-like receptor 7 agonist induces hypoplasia of the biliary system in a neonatal mouse model

作者：Huang Ying Hsien; Shih Hsiang Hung; Tiao Mao Meng; Huang Chao Cheng; Kuo Kuang Che; Huang Fu Chen; Yang Ya Ling; Chuang Jiin Haur^*

来源：Journal of Microbiology, Immunology, and Infection, 2018, 51(2): 166-173.

DOI：10.1016/j.jmii.2016.07.002

• animal model
• Balb/c mice
• biliary atresia
• infantile cholestasis
• innate immunity
• toll-like receptor 7

Background/Purpose: Viral infections and innate immunity signaling, especially Toll-like receptor 7 (TLR7) have been implicated in the pathogenesis of biliary atresia (BA). Administration of rhesus rotavirus-type A to newborn Balb/c mice produces inflammatory obstruction of bile ducts, which resembles human BA. However, whether activation of TLR7 signaling plays a role in neonatal hepatobiliary injury remains to be investigated.
Methods: TLR7 agonist, imiquimod (R837), was intraperitoneally administered to Balb/c mice within 24 hours of birth and then every other day. Morphological and histological injuries of liver and gallbladder were examined at 2 weeks. Hepatic messenger RNA expression of TLR7 signaling was studied. Terminal deoxynucleotidyl transferase 20-deoxyuridine 50-triphosphate nick end labeling staining was used to delineate hepatobiliary apoptosis upon TLR7 stimulation.
Results: TLR7 agonist, imiquimod, induced hypoplasia of the biliary system of neonatal Balb/c mice both in atrophic gallbladder and in paucity of intrahepatic bile ducts. There was significantly higher hepatic expression of TLR7 and downstream innate immunity-mediated interferon regulatory factor 7, interferon-alpha, and tumor necrosis factor-alpha. In addition, terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling-positive cells in the liver were increased after injections of TLR7 agonist.
Conclusion: The results demonstrate that TLR7 activation may trigger innate immunity pathways and induce apoptosis and hypoplasia of neonatal biliary trees in Balb/c mice. The novel findings give an implication of pathogenesis of infantile cholestasis, such as BA.

• 出版日期2018-4
• 单位长春大学