Macroautophagy is essential for killing of intracellular Burkholderia pseudomallei in human neutrophils
Titball, Richard W.
Taylor & Francis
© 2015 Taylor & Francis Group, LLC
Reason for embargo
Neutrophils play a key role in the control of Burkholderia pseudomallei, the pathogen that causes melioidosis. Here, we show that survival of intracellular B. pseudomallei was significantly increased in the presence of 3-methyladenine or lysosomal cathepsin inhibitors. The LC3-flux was increased in B. pseudomallei-infected neutrophils. Concordant with this result, confocal microscopy analyses using anti-LC3 antibodies revealed that B. pseudomallei-containing phagosomes partially overlapped with LC3-positive signal at 3 and 6 h postinfection. Electron microscopic analyses of B. pseudomallei-infected neutrophils at 3 h revealed B. pseudomallei-containing phagosomes that occasionally fused with phagophores or autophagosomes. Following infection with a B. pseudomallei mutant lacking the Burkholderia secretion apparatus Bsa Type III secretion system, neither this characteristic structure nor bacterial escape into the cytosol were observed. These findings indicate that human neutrophils are able to recruit autophagic machinery adjacent to B. pseudomallei-containing phagosomes in a Type III secretion system-dependent manner.
National Institutes of Health: NIAID Cooperative Center 8 for Translational Research on Human Immunology and Biodefense
Thailand Research Fund
This version is the author's peer-reviewed final manuscript. The published version is available from the Taylor & Francis web site http://www.tandfonline.com/ or by following the DOI in this record.
Vol. 11 (5), pp. 748 - 755
U01 AI0 82110
Place of publication