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

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

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

7 Scopus citations

Abstract

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 2′-deoxyuridine 5′-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-α, and tumor necrosis factor-α. 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.

Original languageEnglish
Pages (from-to)166-173
Number of pages8
JournalJournal of Microbiology, Immunology and Infection
Volume51
Issue number2
DOIs
StatePublished - 04 2018

Bibliographical note

Publisher Copyright:
© 2016

Keywords

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

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