Prenylcysteine oxidase 1 like protein is required for neutrophil bactericidal activities.

Autor: Petenkova, Anastasiia, Auger, Shelby A., Lamb, Jeffrey, Quellier, Daisy, Carter, Cody, To, On Tak, Milosevic, Jelena, Barghout, Rana, Kugadas, Abirami, Lu, Xiaoxiao, Geddes-McAlister, Jennifer, Fichorova, Raina, Sykes, David B., Distefano, Mark D., Gadjeva, Mihaela
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Zdroj: Nature Communications; 5/13/2023, Vol. 14 Issue 1, p1-16, 16p
Abstrakt: The bactericidal function of neutrophils is dependent on a myriad of intrinsic and extrinsic stimuli. Using systems immunology approaches we identify microbiome- and infection-induced changes in neutrophils. We focus on investigating the Prenylcysteine oxidase 1 like (Pcyox1l) protein function. Murine and human Pcyox1l proteins share ninety four percent aminoacid homology revealing significant evolutionary conservation and implicating Pcyox1l in mediating important biological functions. Here we show that the loss of Pcyox1l protein results in significant reductions in the mevalonate pathway impacting autophagy and cellular viability under homeostatic conditions. Concurrently, Pcyox1l CRISPRed-out neutrophils exhibit deficient bactericidal properties. Pcyox1l knock-out mice demonstrate significant susceptibility to infection with the gram-negative pathogen Psuedomonas aeruginosa exemplified through increased neutrophil infiltrates, hemorrhaging, and reduced bactericidal functionality. Cumulatively, we ascribe a function to Pcyox1l protein in modulation of the prenylation pathway and suggest connections beween metabolic responses and neutrophil functionality. Neutrophils play critical roles in the response to infection and their function relies on a range of intrinsic and extrinsic factors. Here the authors show a role for Pcyox1l and link this to metabolic pathways including prenylation and the neutrophil response to infection. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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