Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection

Science. 2005 Aug 19;309(5738):1251-3. doi: 10.1126/science.1116006. Epub 2005 Jul 14.

Abstract

Certain pathogens, such as Mycobacterium tuberculosis, survive within the hostile intracellular environment of a macrophage. To identify host factors required for mycobacterial entry and survival within macrophages, we performed a genomewide RNA interference screen in Drosophila macrophage-like cells, using Mycobacterium fortuitum. We identified factors required for general phagocytosis, as well as those needed specifically for mycobacterial infection. One specific factor, Peste (Pes), is a CD36 family member required for uptake of mycobacteria, but not Escherichia coli or Staphylococcus aureus. Moreover, mammalian class B scavenger receptors (SRs) conferred uptake of bacteria into nonphagocytic cells, with SR-BI and SR-BII uniquely mediating uptake of M. fortuitum, which suggests a conserved role for class B SRs in pattern recognition and innate immunity.

Publication types

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

MeSH terms

  • Animals
  • CD36 Antigens / genetics
  • CD36 Antigens / physiology
  • Cell Line
  • Cytoskeleton / physiology
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / microbiology*
  • Drosophila melanogaster / physiology
  • Escherichia coli / physiology
  • Humans
  • Immunity, Innate
  • Lysosomal Membrane Proteins
  • Macrophages / microbiology*
  • Macrophages / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Mice
  • Mycobacterium fortuitum / growth & development
  • Mycobacterium fortuitum / pathogenicity
  • Mycobacterium fortuitum / physiology*
  • Phagocytosis*
  • RNA Interference*
  • RNA, Double-Stranded / pharmacology
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology
  • Receptors, Scavenger
  • Scavenger Receptors, Class B
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / physiology
  • Staphylococcus aureus / physiology
  • Transfection
  • Transport Vesicles / metabolism

Substances

  • CD36 Antigens
  • Lysosomal Membrane Proteins
  • Membrane Proteins
  • RNA, Double-Stranded
  • Receptors, Immunologic
  • Receptors, Scavenger
  • SCARB1 protein, human
  • SCARB2 protein, human
  • Scavenger Receptors, Class B
  • Sialoglycoproteins