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NOBEL PRIZE 2026

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NIHNATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESR01

THE ROLE OF THE NON-CANONICAL INFLAMMASOME IN INNATE IMMUNITY

Completed
Institution
OHIO STATE UNIVERSITY, OH
Principal investigator
Amal O Amer
Funding
$726K
Duration
2021–2026
Open portfolio

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Abstract

ABSTRACT Legionella pneumophila is an infectious bacterium that causes Legionnaire’s disease and remains a major cause of morbidity and mortality in the immunocompromised individuals such as the elderly and cancer patients. Macrophages are the main immune cells that can clear Legionella after activation of the canonical Nlrc4/Naip5 inflammasome. Caspase-11 is a component of the non-canonical inflammasome and mice lacking caspase-11 allow significant Legionella replication in their macrophages. Down-regulation of the homologous caspase in human macrophages increases their permissiveness to Legionella. Our preliminary data show that caspase-11 is necessary for fusion of the Legionella-containing vacuole with the lysosomes via a mechanism that requires the polymerization and depolymerization of actin. Using state-of-the-art techniques including 3D confocal microscopy and high resolution SIM-S microscopy, RNA seq and proteomics analyses, we identified new molecules that are cleaved by caspase-11 and regulate restriction of Legionella in macrophages. This proposal will investigate the molecular mechanisms leading to caspase-11-mediated clearing of Legionella infection.

Research team

  • Amal O AmerPI
  • Stephanie M M SeveauPI

LOADING MOONBASE SCORE

R01NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESInnate Immunity and Inflammation Study Section[III]macrophagescaspaseinflammasomenon-canonicalstate-of-the-art techniquescaspase-vacuolecleaved

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