title: Dangerous Liaisons: Caspase-11 and Reactive Oxygen Species Crosstalk in Pathogen Elimination.
abstract: Recently, the focus of murine caspase-11 and human orthologs caspase-4, -5 research has been on their novel function to induce noncanonical inflammasome activation in direct response to Gram-negative bacterial infection. On the other hand, a new role in anti-bacterial autophagy has been attributed to caspase-11, -4 and -5, which currently stands largely unexplored. In this review, we connect lately emerged evidence that suggests these caspases have a key role in anti-bacterial autophagy and discuss the growing implications of a danger molecule--extracellular ATP--and NADPH oxidase-mediated ROS generation as novel inducers of human caspase-4, -5 signaling during infection. We also highlight the adeptness of persistent pathogens like Porphyromonas gingivalis, a Gram-negative anaerobe and successful colonizer of oral mucosa, to potentially interfere with the activated caspase-4 pathway and autophagy. While, the ability of caspase-4, -5 to promote autophagolysosomal fusion is not well understood, the abundance of caspase-4 in skin and other mucosal epithelial cells implies an important role for caspase-4 in mucosal defense, supporting the view that caspase-4, -5 may play a non-redundant part in innate immunity. Thus, this review will join the currently disconnected cutting-edge research thereby proposing a working model for regulation of caspase-4, -5 in pathogen elimination via cellular-trafficking.
authors.affiliation: Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA. joannroberts@ufl.edu.
authors.forename: JoAnn Simone
authors.initials: JS
authors.lastname: Roberts
authors.affiliation: Department of Periodontology, University of Florida, P.O. Box 100434, Gainesville, FL 32610, USA. oyilmaz@ufl.edu.|Emerging Pathogens Institute, University of Florida, P.O. Box 100434, Gainesville, FL 32610, USA. oyilmaz@ufl.edu.
authors.forename: Ӧzlem
authors.initials: Ӧ
authors.lastname: Yilmaz
mesh_terms: D000818:Animals; D001343:Autophagy; D001419:Bacteria / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D058847:Inflammasomes; D017382:Reactive Oxygen Species; D020169:Caspases
keywords: ATP; Porphyromonas gingivalis; ROS; autophagy; bacteria; caspase-11; caspase-4; caspase-5; infection; inflammasome