Macroautophagy is essential for killing of intracellular Burkholderia pseudomallei in human neutrophils

Darawan Rinchai, Donporn Riyapa, Surachat Buddhisa, Kusumawadee Utispan, Richard W. Titball, Mark P. Stevens, Joanne M. Stevens, Michinaga Ogawa, Isei Tanida, Masato Koike, Yasuo Uchiyama, Manabu Ato, Ganjana Lertmemongkolchai

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17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)748-755
Number of pages8
JournalAutophagy
Volume11
Issue number5
DOIs
Publication statusPublished - 1 Jan 2015
Externally publishedYes

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Keywords

  • Autophagy
  • Burkholderia pseudomallei
  • LC3-II
  • Melioidosis
  • Neutrophils
  • T3SS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Rinchai, D., Riyapa, D., Buddhisa, S., Utispan, K., Titball, R. W., Stevens, M. P., Stevens, J. M., Ogawa, M., Tanida, I., Koike, M., Uchiyama, Y., Ato, M., & Lertmemongkolchai, G. (2015). Macroautophagy is essential for killing of intracellular Burkholderia pseudomallei in human neutrophils. Autophagy, 11(5), 748-755. https://doi.org/10.1080/15548627.2015.1040969