Inflammasome biology taught by Legionella pneumophila

摘要

Inflammasomes are multimeric protein complexes that assemble in the cytosol of many types of cells, including innate immune cells. The inflammasomes can be activated in response to infection or in response to stress signals that induce damage in the host cell membranes. These platforms trigger inflammatory processes, cell death, and the control of microbial replication. Many inflammasomes have been described so far, including NLRP3, NAIP/NLRC4, caspase-11, and AIM2. The ligand for NLRP3 is still unidentified, but the efflux of K+ is essential for NLRP3 activation. By contrast, inflammasomes, such as those composed of NAIP/NLRC4, caspase-11, and AIM2, can be activated by bacterial flagellin, LPS, and dsDNA. The knowledge of inflammasome biology has advanced tremendously in the last decade, fostered by the use of model organisms, such as Legionella pneumophila. This bacterium evolved, infecting unicellular protozoa in freshwater environments, and the human infection is accidental. Thus, L. pneumophila did not evolve sophisticated mechanisms to inhibit mammalian innate immunity. For this reason, it has emerged as a very appropriate model of a pathogenic microbe for the investigation of inflammasome biology. In this review, we highlight the current information regarding the biology of inflammasomes and emphasize the advances achieved using L. pneumophila. We also describe the inflammasomes activated in response to L. pneumophila infection and discuss the effector mechanisms that operate to clear the infection.