Cryptosporidium parvum induces B7-H1 expression in cholangiocytes by down-regulating microRNA-513

J Infect Dis. 2010 Jan 1;201(1):160-9. doi: 10.1086/648589.

Abstract

Expression of B7 costimulatory molecules represents an important compartment of immune response of epithelial cells after microbial infection. We report here that the protozoan parasite Cryptosporidium parvum induced B7-H1 expression in cultured human cholangiocytes. Induced expression of B7-H1 was identified in cells after exposure to infective C. parvum parasite or parasite lysate. Interestingly, the level of microRNA-513 (miR-513) was reduced in cells after exposure to C. parvum, which resulted in a relief of 3' untranslated region-mediated translational suppression of B7-H1. Overexpression of miR-513 through transfection of miR-513 precursor inhibited C. parvum-induced B7-H1 protein expression. Moreover, enhanced apoptotic cell death was identified in activated human T cells after coculture with C. parvum-infected cholangiocytes. The apoptosis of activated T cells was partially blocked by a neutralizing antibody to B7-H1 or transfection of cholangiocytes with miR-513 precursor. These data suggest a role of miR-513 in regulating B7-H1 expression by cholangiocytes in response to C. parvum infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Apoptosis
  • B7-H1 Antigen
  • Bile Ducts / cytology*
  • Bile Ducts / parasitology
  • Cells, Cultured
  • Coculture Techniques
  • Cryptosporidium parvum / pathogenicity*
  • Down-Regulation
  • Epithelial Cells / metabolism*
  • Epithelial Cells / parasitology
  • Humans
  • MicroRNAs / metabolism*
  • T-Lymphocytes / parasitology

Substances

  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • MIRN513A1 microRNA, human
  • MicroRNAs