Decreased expressions of Toll-like receptor 9 and its signaling molecules in chronic hepatitis B virus-infected patients

Arch Pathol Lab Med. 2013 Nov;137(11):1674-9. doi: 10.5858/arpa.2012-0415-OA.

Abstract

Context: Toll-like receptors (TLRs) play crucial roles in immune responses, especially innate immunity, against viral infections. Toll-like receptor 9 recognizes intracellular viral double-strand DNA, which leads to the activation of nuclear factor B (NF-κB) through the myeloid differentiation primary response 88 (MYD88) pathway. Defects in the expression of TLR9 and its signaling molecules may cause attenuated immune responses against hepatitis B virus.

Objective: To determine expression levels of TLR9 messenger RNA along with MYD88, interleukin 1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), and NF-κB in the peripheral blood mononuclear cells obtained from chronic hepatitis B virus (CHB)-infected patients.

Design: In this study, 60 CHB patients and 60 healthy controls were recruited and the expression of TLR9 and its downstream signaling molecules was examined by real-time polymerase chain reaction techniques using β-actin as a housekeeping gene.

Results: Our results showed that expression of TLR9, MYD88, IRAK1, TRAF6, and NF-κB in peripheral blood mononuclear cells of CHB patients was significantly decreased in comparison with healthy controls.

Conclusions: According to our results, it appears that CHB patients are unable to appropriately express genes in the TLR9 pathway, which may impede immune responses against hepatitis B virus infection. These results suggest a mechanism that may partially explain the fact that immune responses are disrupted in CHB patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • DNA, Viral / blood
  • Down-Regulation
  • Female
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / virology
  • Humans
  • Immunity, Innate / genetics
  • Interleukin-1 Receptor-Associated Kinases / genetics
  • Male
  • Middle Aged
  • Myeloid Differentiation Factor 88 / genetics
  • NF-kappa B / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • TNF Receptor-Associated Factor 6 / genetics
  • Toll-Like Receptor 9 / genetics*
  • Viral Load

Substances

  • DNA, Viral
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • RNA, Messenger
  • TLR9 protein, human
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptor 9
  • IRAK1 protein, human
  • Interleukin-1 Receptor-Associated Kinases