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Int. J. Mol. Sci. 2015, 16(10), 23337-23354; doi:10.3390/ijms161023337

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

1
Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA
2
Department of Periodontology, University of Florida, P.O. Box 100434, Gainesville, FL 32610, USA
3
Emerging Pathogens Institute, University of Florida, P.O. Box 100434, Gainesville, FL 32610, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 1 September 2015 / Revised: 23 September 2015 / Accepted: 24 September 2015 / Published: 28 September 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [2262 KB, uploaded 28 September 2015]   |  

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. View Full-Text
Keywords: caspase-11; caspase-4; caspase-5; ROS; autophagy; ATP; bacteria; infection; inflammasome; Porphyromonas gingivalis caspase-11; caspase-4; caspase-5; ROS; autophagy; ATP; bacteria; infection; inflammasome; Porphyromonas gingivalis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Roberts, J.S.; Yilmaz, Ӧ. Dangerous Liaisons: Caspase-11 and Reactive Oxygen Species Crosstalk in Pathogen Elimination. Int. J. Mol. Sci. 2015, 16, 23337-23354.

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