AUTHOR=Harvest Carissa K. , Miao Edward A. 

TITLE=Autophagy May Allow a Cell to Forbear Pyroptosis When Confronted With Cytosol-Invasive Bacteria

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.871190

DOI=10.3389/fimmu.2022.871190

ISSN=1664-3224

ABSTRACT=<p>Inflammatory caspases detect cytosol-invasive Gram-negative bacteria by monitoring for the presence of LPS in the cytosol. This should provide defense against the cytosol-invasive <italic>Burkholderia</italic> and <italic>Shigella</italic> species by lysing the infected cell <italic>via</italic> pyroptosis. However, recent evidence has shown caspase-11 and gasdermin D activation can result in two different outcomes: pyroptosis and autophagy. <italic>Burkholderia cepacia</italic> complex has the ability invade the cytosol but is unable to inhibit caspase-11 and gasdermin D. Yet instead of activating pyroptosis during infection with these bacteria, the autophagy pathway is stimulated through caspases and gasdermin D. In contrast, <italic>Burkholderia thailandensis</italic> can invade the cytosol where caspasae-11 and gasdermin D is activated but the result is pyroptosis of the infected cell. In this review we propose a hypothetical model to explain why autophagy would be the solution to kill one type of <italic>Burkholderia</italic> species, but another <italic>Burkholderia</italic> species is killed by pyroptosis. For pathogens with high virulence, pyroptosis is the only solution to kill bacteria. This explains why some pathogens, such as <italic>Shigella</italic> have evolved methods to inhibit caspase-11 and gasdermin D as well as autophagy. We also discuss similar regulatory steps that affect caspase-1 that may permit the cell to forbear undergoing pyroptosis after caspase-1 activates in response to bacteria with partially effective virulence factors.</p>