Enhancement of neutrophil autophagy by an IVIG preparation against multidrug-resistant bacteria as well as drug-sensitive strains

Hiroshi Itoh, Hidemasa Matsuo, Naoko Kitamura, Sho Yamamoto, Takeshi Higuchi, Hiromu Takematsu, Yasuhiko Kamikubo, Tadakazu Kondo, Kouhei Yamashita, Masataka Sasada, Akifumi Takaori-Kondo, Souichi Adachi

研究成果: ジャーナルへの寄稿学術論文査読

25 被引用数 (Scopus)

抄録

Autophagy occurs in human neutrophils after the phagocytosis of multidrug-resistant bacteria and drug-sensitive strains, including Escherichia coli and Pseudomonas aeruginosa. The present study detected autophagy by immunoblot analysis of LC3B conversion, by confocal scanning microscopic examination of LC3B aggregate formation and by transmission electron microscopic examination of bacteria-containing autophagosomes. Patients with severe bacterial infections are often treated with IVIG alongside antimicrobial agents. Here, we showed that IVIG induced neutrophil-mediated phagocytosis of multidrug-resistant strains. Compared with untreated neutrophils, neutrophils exposed to IVIG showed increased levels of bacterial cell killing, phagocytosis, O2 release, MPO release, and NET formation. IVIG also increased autophagy in these cells. Inhibiting the late phase of autophagy (fusion of lysosomes with autophagosomes) with bafilomycin A1-reduced, neutrophil-mediated bactericidal activity. These findings indicate that autophagy plays a critical role in the bactericidal activity mediated by human neutrophils. Furthermore, the autophagosomes within the neutrophils contained bacteria only and their organelles only, or both bacteria and their organelles, a previously undocumented observation. Taken together, these results suggest that the contents of neutrophil autophagosomes may be derived from specific autophagic systems, which provide the neutrophil with an advantage. Thus, IVIG promotes the neutrophil-mediated killing of multidrug-resistant bacteria as well as drug-sensitive strains.

本文言語英語
ページ(範囲)107-117
ページ数11
ジャーナルJournal of Leukocyte Biology
98
1
DOI
出版ステータス出版済み - 01-07-2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学
  • 細胞生物学

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