Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking

Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6193-8. doi: 10.1073/pnas.1117490109. Epub 2012 Apr 2.


Legionella pneumophila, the causative agent of Legionnaires' pneumonia, resides in a distinct vacuole structure called Legionella-containing vacuole (LCV). The LCV resists fusion with the lysosome and permits efficient bacterial replication in host macrophages, which requires a Dot/Icm type IVB secretion system. Dot/Icm-translocated effector SdhA is critical for L. pneumophila intracellular growth and functions to prevent host cell death. Here, we show that the absence of SdhA resulted in elevated caspase-1 activation and IL-1β secretion as well as macrophage pyroptosis during Legionella infection. These inflammasome activation phenotypes were independent of the established flagellin-NAIP5-NLRC4 axis, but relied on the DNA-sensing AIM2 inflammasome. We further demonstrate that Legionella DNA was released into macrophage cytosol, and this effect was significantly exaggerated by the absence of SdhA. SdhA bears a functional Golgi-targeting GRIP domain that is required for preventing AIM2 inflammasome activation. Ectopically expressed SdhA formed a unique ring-shape membrane structure, further indicating a role in membrane trafficking and maintaining LCV membrane integrity. Our data together suggest a possible link, mediated by the function of SdhA, between LCV trafficking/maturation and suppression of host innate immune detection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biological Transport
  • Caspase 1 / metabolism
  • Cell Line
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism*
  • DNA-Binding Proteins
  • Flavoproteins / genetics
  • Flavoproteins / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Immunoblotting
  • Inflammasomes / metabolism*
  • Intracellular Membranes / metabolism
  • Legionella pneumophila / genetics
  • Legionella pneumophila / metabolism*
  • Legionella pneumophila / physiology
  • Lysosomes / metabolism
  • Lysosomes / microbiology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Interference
  • U937 Cells
  • Vacuoles / metabolism
  • Vacuoles / microbiology


  • Aim2 protein, mouse
  • Bacterial Proteins
  • DNA, Bacterial
  • DNA-Binding Proteins
  • Flavoproteins
  • Inflammasomes
  • Nuclear Proteins
  • SdhA protein, Bacteria
  • Caspase 1