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Prenylcysteine oxidase 1 like protein is required for neutrophil bactericidal activities

ABSTRACT: The bactericidal function of neutrophils are dependent on myriad intrinsic and extrinsic stimuli. Using systems immunology approaches we identified microbiome- and infection-induced changes in neutrophils. We focused 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 P. aeruginosa exemplified through increased neutrophil infiltrates, hemorrhaging, and reduced bactericidal functionality. Cumulatively, we ascribe a function to Pcyox1l protein as a fundamental regulator of the prenylation pathway and suggest connections beween metabolic responses and neutrophil functionality. Anastasia Petenkova , Shelby A. Auger, Jeffrey Lamb, Daisy Quellier, Cody Carter, On TakTo, Jelena Milosevic, Rana Barghout, Abirami Kugadas, Xiaoxiao Lu, Jennifer Geddes-McAlister, Raina Fichorova, David B. Sykes, Mark D. Distefano, and Mihaela Gadjeva. 2023. Prenylcysteine oxidase 1 like protein is required for neutrophil bactericidal activities. Nat.Comm.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Neutrophil

SUBMITTER: Shelby Auger

LAB HEAD: Mark, D, Distefano

PROVIDER: PXD031115 | Pride | 2023-04-14

REPOSITORIES: Pride

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