Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection.
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.
Philips
Jennifer A
JA
Department of Genetics, Harvard Medical School, 77 Louis Pasteur Avenue, Boston, MA 02115, USA. jphilips@partners.org
Rubin
Eric J
EJ
Perrimon
Norbert
N
D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D003599:Cytoskeleton / Q000502:physiology; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000382:microbiology* / Q000502:physiology; D004926:Escherichia coli / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D051907:Lysosomal Membrane Proteins; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D019907:Mycobacterium fortuitum / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D010587:Phagocytosis; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012795:Sialoglycoproteins / Q000235:genetics / Q000502:physiology; D013211:Staphylococcus aureus / Q000502:physiology; D014162:Transfection; D022161:Transport Vesicles / Q000378:metabolism
D018955:CD36 Antigens; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D012330:RNA, Double-Stranded; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C074299:SCARB2 protein, human; D051122:Scavenger Receptors, Class B; D012795:Sialoglycoproteins