Efferocytosis is an innate antibacterial mechanism

Details

• Alternative Title:
  Cell Host Microbe
• Personal Author:
  Martin, Constance J. ; Booty, Matthew G. ; Rosebrock, Tracy R. ; Nunes-Alves, Cláudio ; Desjardins, Danielle M. ; Keren, Iris ; Fortune, Sarah M. ; Remold, Heinz G. ; Behar, Samuel M.
• Description:
  Mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. We find that after apoptosis, M. tuberculosis-infected macrophages are rapidly taken up by uninfected macrophages through efferocytosis, a dedicated apoptotic cell engulfment process. Efferocytosis of M. tuberculosis sequestered within an apoptotic macrophage further compartmentalizes the bacterium and delivers it along with the apoptotic cell debris to the lysosomal compartment. M. tuberculosis is killed only after efferocytosis, indicating that apoptosis itself is not intrinsically bactericidal but requires subsequent phagocytic uptake and lysosomal fusion of the apoptotic body harboring the bacterium. While efferocytosis is recognized as a constitutive housekeeping function of macrophages, these data indicate that it can also function as an antimicrobial effector mechanism.
• Subjects:
  Animals Apoptosis Cells, Cultured Immune Evasion Lysosomes Macrophages Mice Mice, Inbred C57BL Microbial Viability Microscopy, Electron, Transmission Microscopy, Fluorescence Mycobacterium Tuberculosis Phagocytosis

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• Source:
  Cell Host Microbe. 2012; 12(3):289-300.
• Pubmed ID:
  22980326
• Pubmed Central ID:
  PMC3517204
• Document Type:
  Journal Article
• Funding:
  5P30AI060354/AI/NIAID NIH HHS/United States ; DP2-0D001378/DP/NCCDPHP CDC HHS/United States ; P30 AI060354/AI/NIAID NIH HHS/United States ; R01 AI098637/AI/NIAID NIH HHS/United States ; R01AI072143/AI/NIAID NIH HHS/United States ; R56AI084161/AI/NIAID NIH HHS/United States ; T32 AI007387/AI/NIAID NIH HHS/United States ; T32-AI07387/AI/NIAID NIH HHS/United States ; TL1 RR029881/RR/NCRR NIH HHS/United States ; UL1 RR029882/RR/NCRR NIH HHS/United States
• Volume:
  12
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:f88c9593cd8892587dda191de29931b6d32f521f6664cacc4ee8cba8159b503a
• Download URL:
  https://stacks.cdc.gov/view/cdc/33487/cdc_33487_DS1.pdf
• File Type:
  [PDF - 4.35 MB ]