PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection
Parkinson's disease is characterized by a period of non-motor symptoms, including gastrointestinal dysfunction, preceding motor deficits by several years to decades. This long prodrome is suggestive of peripheral immunity involvement in the initiation of disease. We previously developed a model system in PINK1 KO mice displaying PD-like motor symptoms at late stages following intestinal infections. Herein, we map the initiating immune events at the site of infection in this model. Using single-cell RNAseq, we demonstrate that peripheral myeloid cells are the earliest highly dysregulated immune cell type followed by an aberrant T cell response shortly after. We also demonstrate an increased propensity for antigen presentation and that activated myeloid cells acquire a proinflammatory profile capable of inducing cytotoxic T cell responses. Together, our study provides the first evidence that PINK1 is a key regulator of immune functions in the gut underlying early PD-related disease mechanisms.
Authors
- Hicham Bessaiah (ORCID: https://orcid.org/0000-0001-7333-2581)
- Elia Afanasiev (ORCID: https://orcid.org/0000-0002-6527-4550)
- Samantha Gruenheid (ORCID: https://orcid.org/0000-0002-0908-6715)
- Alexandra Kazanova (ORCID: https://orcid.org/0000-0003-4850-9845)
- Jessica Pei (ORCID: https://orcid.org/0000-0001-7115-5606)
- Alexis Allot (ORCID: https://orcid.org/0000-0002-2706-9054)
- Louis‐Éric Trudeau (ORCID: https://orcid.org/0000-0003-4684-1377)
- Shinjini Mukherjee (ORCID: https://orcid.org/0000-0001-9206-8739)
- Sherilyn Junelle Recinto (ORCID: https://orcid.org/0000-0001-9632-1201)
- Brendan Cordeiro (ORCID: https://orcid.org/0000-0001-5677-0686)
- Diana Matheoud (ORCID: https://orcid.org/0000-0001-5574-315X)
- Jo Anne Stratton (ORCID: https://orcid.org/0000-0002-1205-1353)
- Heidi M. McBride (ORCID: https://orcid.org/0000-0003-4666-2280)
- Adam MacDonald (ORCID: https://orcid.org/0000-0002-6470-1186)
- Moein Yaqubi (ORCID: https://orcid.org/0000-0001-7299-5930)
- Shobina Premachandran (ORCID: https://orcid.org/0009-0002-0672-1362)
- Lin Liu (ORCID: https://orcid.org/0000-0001-7314-4425)
Institutions
- Montreal Neurological Institute and Hospital (CA)
- Research Network (United States) (US)
- McGill University (CA)
- Université de Montréal (CA)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1038/s41531-025-00945-w
- Citations
- 5
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 4.21
Funders
- Michael J. Fox Foundation for Parkinson's Research
- Canadian Institutes of Health Research