PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection
Abstract 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 m...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-025-00945-w |
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| author | Sherilyn Junelle Recinto Alexandra Kazanova Lin Liu Brendan Cordeiro Shobina Premachandran Hicham Bessaiah Alexis Allot Elia Afanasiev Sriparna Mukherjee Jessica Pei Adam MacDonald Moein Yaqubi Heidi M. McBride Diana Matheoud Louis-Eric Trudeau Samantha Gruenheid Jo Anne Stratton |
| author_facet | Sherilyn Junelle Recinto Alexandra Kazanova Lin Liu Brendan Cordeiro Shobina Premachandran Hicham Bessaiah Alexis Allot Elia Afanasiev Sriparna Mukherjee Jessica Pei Adam MacDonald Moein Yaqubi Heidi M. McBride Diana Matheoud Louis-Eric Trudeau Samantha Gruenheid Jo Anne Stratton |
| author_sort | Sherilyn Junelle Recinto |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-6ec99c2cc2e94d41962056a58643dc5e |
| institution | OA Journals |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-6ec99c2cc2e94d41962056a58643dc5e2025-08-20T02:34:06ZengNature Portfolionpj Parkinson's Disease2373-80572025-05-0111111610.1038/s41531-025-00945-wPINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infectionSherilyn Junelle Recinto0Alexandra Kazanova1Lin Liu2Brendan Cordeiro3Shobina Premachandran4Hicham Bessaiah5Alexis Allot6Elia Afanasiev7Sriparna Mukherjee8Jessica Pei9Adam MacDonald10Moein Yaqubi11Heidi M. McBride12Diana Matheoud13Louis-Eric Trudeau14Samantha Gruenheid15Jo Anne Stratton16Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityDepartment of Microbiology and Immunology, McGill UniversityDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityDepartment of Microbiology and Immunology, McGill UniversityDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityDepartment of Neuroscience, Faculty of Medicine, Université de MontréalAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityAbstract 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.https://doi.org/10.1038/s41531-025-00945-w |
| spellingShingle | Sherilyn Junelle Recinto Alexandra Kazanova Lin Liu Brendan Cordeiro Shobina Premachandran Hicham Bessaiah Alexis Allot Elia Afanasiev Sriparna Mukherjee Jessica Pei Adam MacDonald Moein Yaqubi Heidi M. McBride Diana Matheoud Louis-Eric Trudeau Samantha Gruenheid Jo Anne Stratton PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection npj Parkinson's Disease |
| title | PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection |
| title_full | PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection |
| title_fullStr | PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection |
| title_full_unstemmed | PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection |
| title_short | PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection |
| title_sort | pink1 deficiency rewires early immune responses in a mouse model of parkinson s disease triggered by intestinal infection |
| url | https://doi.org/10.1038/s41531-025-00945-w |
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