S100A10 downregulation inhibits the phagocytosis of Cryptococcus neoformans by murine brain microvascular endothelial cells

Microb Pathog. 2011 Sep;51(3):96-100. doi: 10.1016/j.micpath.2011.05.003. Epub 2011 May 20.

Abstract

Cryptococcus neoformans invades the central nerve system through endocytosis by the vascular endothelia. S100A10 interacts with Ca(2+) channel proteins in the vascular endothelia and regulates the filamentous actin network. We hypothesized that S100A10 was involved in the pathogenesis of cryptococcosis and sought to investigate here the effect on the phagocytosis and growth of C. neoformans of S100A10 downregulation by small interfering RNA in murine brain microvascular endothelial cell (MBMECs). We found that S100A10 downregulation significantly reduced the intracellular Ca(2+) concentration (P < 0.05). Additionally, suppression of S100A10 expression was associated with significantly reduced rate of phagocytosis and budding of C. neoformans. The capsule of intracellular C. neoformans also became thicker after S100A10 was knocked down. The findings demonstrated that knockdown of S100A10 in MBMEC could attenuate the growth of intracellular C. neoformans. We inferred that the S100A10 may play an important role in transpenetration of C. neoformans across the vascular endothelia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A2 / antagonists & inhibitors
  • Annexin A2 / immunology*
  • Brain / immunology
  • Brain / microbiology
  • Calcium / analysis
  • Cryptococcus neoformans / immunology*
  • Cryptococcus neoformans / pathogenicity*
  • Cytosol / chemistry
  • Endothelial Cells / immunology*
  • Endothelial Cells / microbiology*
  • Gene Knockdown Techniques
  • Gene Silencing
  • Mice
  • Phagocytosis*
  • RNA, Small Interfering / metabolism
  • S100 Proteins / antagonists & inhibitors
  • S100 Proteins / immunology*

Substances

  • Annexin A2
  • RNA, Small Interfering
  • S100 Proteins
  • S100 calcium binding protein A10
  • Calcium