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Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with lysosomes by modulating actin

Anwari Akhter1, Kyle Caution, Arwa Abu Khweek

  • 1Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA.

Immunity
|June 5, 2012
PubMed

Insights

Caspase-11 is crucial for restricting Legionella pneumophila infection by promoting vacuole-lysosome fusion in macrophages. This inflammasome component plays a key role in innate immunity against specific bacterial pathogens.

Area of Science:

  • Innate immunity
  • Cellular microbiology
  • Inflammasome signaling

Background:

  • Inflammasomes are multiprotein complexes involving NLRs and caspase-1, activated by bacterial molecules in macrophages.
  • Caspase-11 activates caspase-1 in response to LPS and bacterial toxins, but its role in bacterial infection is unclear.

Purpose of the Study:

  • To investigate the role of caspase-11 in host defense against bacterial infections.
  • To determine if caspase-11 is required for caspase-1 activation during infection with various bacteria.
  • To elucidate the mechanism by which caspase-11 restricts bacterial pathogens.

Main Methods:

  • Assessing caspase-1 activation in response to bacterial infection.
  • Evaluating the requirement of active caspase-11 for restricting bacterial pathogens like Legionella pneumophila.
  • Analyzing the effect of caspase-11 on phagosome-lysosome trafficking and actin polymerization.

Main Results:

  • Caspase-11 was dispensable for caspase-1 activation by Legionella, Salmonella, Francisella, and Listeria.
  • Active mouse caspase-11 was essential for restricting Legionella pneumophila infection.
  • Human caspase-4 and caspase-5 homologs also restricted L. pneumophila in human macrophages.
  • Caspase-11 modulated actin polymerization via cofilin, promoting fusion of L. pneumophila vacuoles with lysosomes.
  • Caspase-11 did not affect lysosome fusion with phagosomes containing nonpathogenic bacteria.

Conclusions:

  • Caspase-11 plays a critical role in innate immunity against Legionella pneumophila, independent of caspase-1 activation.
  • Caspase-11 restricts bacterial infection by enhancing phagosome-lysosome fusion through cofilin-mediated actin modulation.
  • Phagosome trafficking is cargo-dependent, with caspase-11 distinguishing between pathogenic and nonpathogenic bacterial phagosomes.

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