Neutrophil-generated HOCI leads to non-specific thiol oxidation in phagocytized bacteria

作者：Degrossoli Adriana; Mueller Alexandra; Xie Kaibo; Schneider Jannis F; Bader Verian; Winklhofer Konstanze F; Meyer Andreas J; Leichert Lars I^*

来源：eLife, 2018, 7: e32288.

DOI：10.7554/eLife.32288

Phagocytic immune cells kill pathogens in the phagolysosomal compartment with a cocktail of antimicrobial agents. Chief among them are reactive species produced in the so-called oxidative burst. Here, we show that bacteria exposed to a neutrophil-like cell line experience a rapid and massive oxidation of cytosolic thiols. Using roGFP2-based fusion probes, we could show that this massive breakdown of the thiol redox homeostasis was dependent on phagocytosis, presence of NADPH oxidase and ultimately myeloperoxidase. Interestingly, the redox-mediated fluorescence change in bacteria expressing a glutathione-specific Grxl-roGFP2 fusion protein or an unfused roGFP2 showed highly similar reaction kinetics to the ones observed with roGFP2-Orpl, under all conditions tested. We recently observed such an indiscriminate oxidation of roGFP2based fusion probes by HOCI with fast kinetics in vitro. In line with these observations, abating HOCI production in immune cells with a myeloperoxidase inhibitor significantly attenuated the oxidation of all three probes in bacteria.

• 出版日期2018-3-6