The antimicrobial cathelicidin peptide hlF(1-11) attenuates alveolar macrophage pyroptosis induced by Acinetobacter baumannii in vivo

Exp Cell Res. 2018 Mar 1;364(1):95-103. doi: 10.1016/j.yexcr.2018.01.035. Epub 2018 Feb 1.

Abstract

Acinetobacter baumannii is a Gram-negative coccobacillus found primarily in hospital settings that has recently emerged as a source of hospital-acquired infections, including bacterial pneumonia. The hLF(1-11) peptide comprising the first 11 N-terminal residues of human lactoferrin exerts antimicrobial activity in vivo and was highly effective against multidrug-resistant A. baumannii strains in vitro and in vivo. Pyroptosis is a caspase-1-dependent inflammatory cell death process and is induced by various microbial infections. In the present study, we investigated the molecular mechanisms that regulate pyroptosis induced by A. baumannii in macrophages. Our results revealed that A. baumannii induced pyroptosis through caspase-1 activation and IL-1β production. We also found that caspase-1 activation and IL-1β maturation in A. baumannii-triggered pyroptotic cell death were reduced by hLF(1-11) treatment. Moreover, hLF(1-11) inhibited the A. baumannii-induced caspase-1 activation and pyroptosis of pulmonary alveolar macrophages in vivo.

Keywords: Acinetobacter baumannii; Caspase-1; Pyroptosis; hLF(1-11).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / drug therapy*
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects*
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Apoptosis / drug effects
  • Cathelicidins
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Humans
  • Inflammasomes / drug effects
  • Lactoferrin / pharmacology*
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / microbiology
  • Macrophages, Alveolar / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / pharmacology*
  • Pyroptosis / drug effects*

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Inflammasomes
  • Peptide Fragments
  • lactoferrin (1-11), human
  • Lactoferrin
  • Cathelicidins