@article{d49a28269fc1479bbea41156abc23269,
title = "CASP4/caspase-11 promotes autophagosome formation in response to bacterial infection",
abstract = "CASP4/caspase-11-dependent inflammasome activation is important for the clearance of various Gram-negative bacteria entering the host cytosol. Additionally, CASP4 modulates the actin cytoskeleton to promote the maturation of phagosomes harboring intracellular pathogens such as Legionella pneumophila but not those enclosing nonpathogenic bacteria. Nevertheless, this non-inflammatory role of CASP4 regarding the trafficking of vacuolar bacteria remains poorly understood. Macroautophagy/autophagy, a catabolic process within eukaryotic cells, is also implicated in the elimination of intracellular pathogens such as Burkholderia cenocepacia. Here we show that CASP4-deficient macrophages exhibit a defect in autophagosome formation in response to B. cenocepacia infection. The absence of CASP4 causes an accumulation of the small GTPase RAB7, reduced colocalization of B. cenocepacia with LC3 and acidic compartments accompanied by increased bacterial replication in vitro and in vivo. Together, our data reveal a novel role of CASP4 in regulating autophagy in response to B. cenocepacia infection.",
keywords = "Burkholderia cenocepacia, autophagy, caspase-1 (CASP1), caspase-11 (CASP4), lysosome, macrophages",
author = "Kathrin Krause and Kyle Caution and Asmaa Badr and Kaitlin Hamilton and Abdulmuti Saleh and Khushbu Patel and Stephanie Seveau and Luanne Hall-Stoodley and Rana Hegazi and Xiaoli Zhang and Gavrilin, {Mikhail A.} and Amer, {Amal O.}",
note = "Funding Information: This work was supported by the | NIH | National Institute of Allergy and Infectious Diseases (NIAID) [R01AI24121];HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) [R21AI113477]; | NIH | National Heart, Lung, and Blood Institute (NHBLI) [R01HL127651-01A1] We thank M. Valvano at Queen?s University, Belfast, UK for providing red fluorescent B. cenocepacia and B. cenocepacia ?T6SS strains. We thank Daniel M. Layman, Mohamed Quteifan, and Anup Vaidya for technical help. We are grateful to Dr. Sue E. Knoblaugh at the College of Veterinary Medicine/Department of Veterinary Biosciences at the Ohio State University, Columbus OH, USA for the histological evaluation of lung tissue. Comparative Pathology & Mouse Phenotyping Shared Resource, Department of Veterinary Biosciences and the Comprehensive Cancer Center, The Ohio State University, are supported in part by grant P30 CA016058. Studies in the Amer laboratory are supported by Ohio State University (OSU) Bridge funds, Public Health Preparedness for Infectious Diseases (PHPID), Center for Clinical and Translational Science (CCTS), R21 AI113477, R01 AI24121, and R01 HL127651-01A1. Cytokine analysis using the V-PLEX Proinflammatory Panel 1 (mouse) Kit was supported by Award Number Grant UL1TR001070 from the National Center For Advancing Translational Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Advancing Translational Sciences or the National Institutes of Health. KK is supported by Deutsche Forschungsgemeinschaft (DFG - German Research Foundation). KC is supported by a Cystic Fibrosis Foundation Postdoctoral Research Fellowship. AB is supported by funding from the Egyptian Government. The authors declare that they have no conflict of interests. Funding Information: This work was supported by the | NIH | National Institute of Allergy and Infectious Diseases (NIAID) [R01AI24121];HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) [R21AI113477]; | NIH | National Heart, Lung, and Blood Institute (NHBLI) [R01HL127651-01A1] Funding Information: We thank M. Valvano at Queen{\textquoteright}s University, Belfast, UK for providing red fluorescent B. cenocepacia and B. cenocepacia ΔT6SS strains. We thank Daniel M. Layman, Mohamed Quteifan, and Anup Vaidya for technical help. We are grateful to Dr. Sue E. Knoblaugh at the College of Veterinary Medicine/Department of Veterinary Biosciences at the Ohio State University, Columbus OH, USA for the histological evaluation of lung tissue. Comparative Pathology & Mouse Phenotyping Shared Resource, Department of Veterinary Biosciences and the Comprehensive Cancer Center, The Ohio State University, are supported in part by grant P30 CA016058. Studies in the Amer laboratory are supported by Ohio State University (OSU) Bridge funds, Public Health Preparedness for Infectious Diseases (PHPID), Center for Clinical and Translational Science (CCTS), R21 AI113477, R01 AI24121, and R01 HL127651-01A1. Cytokine analysis using the V-PLEX Proinflammatory Panel 1 (mouse) Kit was supported by Award Number Grant UL1TR001070 from the National Center For Advancing Translational Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Advancing Translational Sciences or the National Institutes of Health. KK is supported by Deutsche Forschungsgemeinschaft (DFG - German Research Foundation). KC is supported by a Cystic Fibrosis Foundation Postdoctoral Research Fellowship. AB is supported by funding from the Egyptian Government. The authors declare that they have no conflict of interests. Publisher Copyright: {\textcopyright} 2018, {\textcopyright} 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",
year = "2018",
month = nov,
day = "2",
doi = "10.1080/15548627.2018.1491494",
language = "English (US)",
volume = "14",
pages = "1928--1942",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "11",
}