Peroxidasin contributes to lung host defense by direct binding and killing of gram-negative bacteria

PLoS Pathogens
Ruizheng ShiGuangjie Cheng

Abstract

Innate immune recognition is classically mediated by the interaction of host pattern-recognition receptors and pathogen-associated molecular patterns; this triggers a series of downstream signaling events that facilitate killing and elimination of invading pathogens. In this report, we provide the first evidence that peroxidasin (PXDN; also known as vascular peroxidase-1) directly binds to gram-negative bacteria and mediates bactericidal activity, thus, contributing to lung host defense. PXDN contains five leucine-rich repeats and four immunoglobulin domains, which allows for its interaction with lipopolysaccharide, a membrane component of gram-negative bacteria. Bactericidal activity of PXDN is mediated via its capacity to generate hypohalous acids. Deficiency of PXDN results in a failure to eradicate Pseudomonas aeruginosa and increased mortality in a murine model of Pseudomonas lung infection. These observations indicate that PXDN mediates previously unrecognized host defense functions against gram-negative bacterial pathogens.

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Citations

Jul 18, 2020·The Journal of Biological Chemistry·Boushra BathishChristine C Winterbourn
Mar 8, 2020·Journal of Clinical Medicine·Pauline CaillardDimitri Titeca-Beauport
Apr 27, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sarah McCarronTobias D Raabe
Jan 13, 2022·Microbiology Spectrum·Zehong Cao, Guangjie Cheng

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Methods Mentioned

BETA
surface plasmon resonance
bronchoalveolar lavage
RNA-seq
Fluorescence
phase contrast microscopy
bronchoalveolar
lavage
Chip

Software Mentioned

BIAevaluation
Biacore T200
Biacore
ImageJ

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