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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD36 Antigens / genetics
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CD36 Antigens / physiology
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Cell Line
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Cytoskeleton / physiology
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Drosophila melanogaster / cytology
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Drosophila melanogaster / genetics
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Drosophila melanogaster / microbiology*
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Drosophila melanogaster / physiology
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Escherichia coli / physiology
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Humans
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Immunity, Innate
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Lysosomal Membrane Proteins
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Macrophages / microbiology*
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Macrophages / physiology
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Membrane Proteins / genetics
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Membrane Proteins / physiology
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Mice
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Mycobacterium fortuitum / growth & development
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Mycobacterium fortuitum / pathogenicity
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Mycobacterium fortuitum / physiology*
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Phagocytosis*
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RNA Interference*
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RNA, Double-Stranded / pharmacology
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Receptors, Immunologic / genetics
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Receptors, Immunologic / physiology
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Receptors, Scavenger
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Scavenger Receptors, Class B
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Sialoglycoproteins / genetics
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Sialoglycoproteins / physiology
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Staphylococcus aureus / physiology
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Transfection
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Transport Vesicles / metabolism
Substances
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CD36 Antigens
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Lysosomal Membrane Proteins
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Membrane Proteins
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RNA, Double-Stranded
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Receptors, Immunologic
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Receptors, Scavenger
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SCARB1 protein, human
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SCARB2 protein, human
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Scavenger Receptors, Class B
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Sialoglycoproteins