The inflammasome: Learning from bacterial evasion strategies.
The innate immune system plays a critical role in defense against microbial infection and employs germline-encoded pattern recognition receptors to detect broadly conserved microbial structures or activities. Pattern recognition receptors of the nucleotide binding domain/leucine rich repeat (NLR) family respond to particular microbial products or disruption of cellular physiology, and mediate the activation of an arm of the innate immune response termed the inflammasome. Inflammasomes are multiprotein complexes that are inducibly assembled in response to the contamination of the host cell cytosol by microbial products. Individual NLRs sense the presence of their cognate stimuli, and initiate assembly of inflammasomes via the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and the effector pro-enzyme caspase-1. Inflammasome activation leads to rapid release of pro-inflammatory mediators of the IL-1 family as well as the release of intracellular alarmins due to a lytic form of programmed cell death termed pyroptosis. Over the past 15 years, a great deal has been learned about the mechanisms that drive inflammasome activation in response to infection by diverse pathogens. However, pathogens have also evolved mechanisms to evade or suppress host defenses, and the mechanisms by which pathogens evade inflammasome activation are not well-understood. Here, we will discuss emerging evidence on how diverse pathogens evade inflammasome activation, and what these studies have revealed about inflammasome biology. Deeper understanding of pathogen evasion of inflammasome activation has the potential to lead to development of novel classes of immunomodulatory factors that could be used in the context of human inflammatory diseases.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: sunshin@mail.med.upenn.edu.
Sunny
S
Shin
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: ibrodsky@vet.upenn.edu.
Igor E
IE
Brodsky
D000818:Animals; D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D058847:Inflammasomes / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000276:immunology
D058847:Inflammasomes; D051192:Receptors, Pattern Recognition
Caspase-1; Inflammasome; Microbial evasion; Salmonella; Yersinia