Evidence map›Paper›PMID 42463806›Full record

ArticleCellular & molecular immunology2026

The Parkinson's disease-linked G2019S mutation of LRRK2 increases NADPH oxidase-2 activity in neutrophils for superior control of bacterial infections.

Kate Hurley, Rachel Kaul, Sahil Yadav, Dikchha Rijal, Leila Sam, Avni Bhan, Rayan El Hamra, Ardeshir Ariana, Adam Mahdi, Willem Brandt and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular & molecular immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Kate HurleyDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
Rachel KaulDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
Sahil YadavDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
Dikchha RijalDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
Leila SamDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
Avni BhanDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
Rayan El HamraDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
Ardeshir ArianaDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
Adam MahdiDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
Willem BrandtDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
Julianna J TomlinsonProgram in Neuroscience, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
Michael G SchlossmacherProgram in Neuroscience, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
Subash SadDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada. Subash.sad@uottawa.ca.ORCID 0000-0002-2462-7137

Funding

Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) PJT-185880
6 · The paper itself

Abstract

Allelic variants in the leucine-rich repeat kinase-2 (LRRK2) gene are linked to Parkinson's disease, Crohn's disease and leprosy; however, a consensus role of LRRK2 in infection has not yet emerged. Parkinson's disease-linked p.G2019S mutation of LRRK2 results in increased kinase activity. We evaluated the impact of the p.G2019S mutation during the infection of mice with Salmonella typhimurium (ST) or Listeria monocytogenes. We demonstrate that the p.G2019S mutation promotes the phosphorylation of the p40phox and p47phox subunits of the NADPH oxidase-2 complex in the cytosol of neutrophils, leading to their relocation to lysosomes for enhanced bacterial control. Activation of Cathepsin B, Rab10 or PKC was not modulated by p.G2019S. Activation of the cytosolic subunits of NADPH oxidase-2 subunits was inhibited by the virulence factor SifA, which promotes the phagosomal localization of ST. Deletion of SifA resulted in an even greater effect of the p.G2019S mutation on the control of ST by neutrophils. These results suggest a mechanism by which the p.G2019S mutation promotes better control of infections at the cost of excessive tissue damage via NADPH oxidase-2 activity under chronic inflammatory conditions.

Indexed as

Bacterial InfectionsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2ListeriosisMutationNADPH Oxidase 2NeutrophilsParkinson DiseaseSalmonella InfectionsAnimalsHumansListeria monocytogenesLysosomesMiceMice, Inbred C57BLNADPH OxidasesPhosphoproteinsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Lrrk2 protein, mouseNADPH Oxidase 2NADPH Oxidasesneutrophil cytosol factor 40Kneutrophil cytosolic factor 1PhosphoproteinsVirulence FactorsInnate immunityNeutrophil functionNOX2 activationParkinson’s disease: Lrrk2 mutationReactive oxygen species

Identifiers

PMID42463806
PMCPMC13526855

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.