Absence of CD14 Delays Progression of Prion Diseases Accompanied by Increased Microglial Activation

• Sakai, Keiko

• Hasebe, Rie

• Takahashi, Yusuke

• Song, Chang-Hyun

• Suzuki, Akio

• Yamasaki, Takeshi

• Horiuchi, Motohiro

Abstract

Prion diseases are fatal neurodegenerative disorders characterized by accumulation of PrPSc, vacuolation of neurons and neuropil, astrocytosis, and microglial activation. Upregulation of gene expressions of innate immunity-related factors, including complement factors and CD14, is observed in the brains of mice infected with prions even in the early stage of infections. When CD14 knockout (CD14(-/-)) mice were infected intracerebrally with the Chandler and Obihiro prion strains, the mice survived longer than wild-type (WT) mice, suggesting that CD14 influences the progression of the prion disease. Immunofluorescence staining that can distinguish normal prion protein from the disease-specific form of prion protein (PrPSc) revealed that deposition of PrPSc was delayed in CD14(-/-) mice compared with WT mice by the middle stage of the infection. Immunohistochemical staining with Iba1, a marker for activated microglia, showed an increased microglial activation in prion-infected CD14(-/-) mice compared to WT mice. Interestingly, accompanied by the increased microglial activation, anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta) appeared to be expressed earlier in prion-infected CD14(-/-) mice. In contrast, IL-1 beta expression appeared to be reduced in the CD14(-/-) mice in the early stage of infection. Double immunofluorescence staining demonstrated that CD11b- and Iba1-positive microglia mainly produced the anti-inflammatory cytokines, suggesting anti-inflammatory status of microglia in the CD14(-/-) mice in the early stage of infection. These results imply that CD14 plays a role in the disease progression by suppressing anti-inflammatory responses in the brain in the early stage of infection.

Journal

• Journal of Virology

  Journal of Virology 87 (24), 13433-13445, 2013-12

  American Society for Microbiology

Details

• CRID: 1050001202677760896
• NII Article ID: 120005455879
• HANDLE: 2115/56527
• ISSN: 0022538X
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles