Dangerous Liaisons: Caspase-11 and Reactive Oxygen Species Crosstalk in Pathogen Elimination

International Journal of Molecular Sciences

JoAnn Simone Roberts¹  Ӧzlem Yilmaz² 

[1] Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA;Department of Periodontology, University of Florida, P.O. Box 100434, Gainesville, FL 32610, USA

关键词: caspase-11;    caspase-4;    caspase-5;    ROS;    autophagy;    ATP;    bacteria;    infection;    inflammasome;    Porphyromonas gingivalis;   

DOI  :  10.3390/ijms161023337

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.