Immunotherapy targeting the PD-1 pathway alleviates neuroinflammation caused by chronic Toxoplasma infection
Abstract Toxoplasma gondii can infect the host brain and trigger neuroinflammation. Such neuroinflammation might persist for years if the infection is not resolved, resulting in harmful outcomes for the brain. We have previously demonstrated the efficacy of immunotherapy targeting the programmed cel...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-28322-8 |
| _version_ | 1811175878129876992 |
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| author | Jianchun Xiao Ye Li Treva Rowley Jing Huang Robert H. Yolken Raphael P. Viscidi |
| author_facet | Jianchun Xiao Ye Li Treva Rowley Jing Huang Robert H. Yolken Raphael P. Viscidi |
| author_sort | Jianchun Xiao |
| collection | DOAJ |
| description | Abstract Toxoplasma gondii can infect the host brain and trigger neuroinflammation. Such neuroinflammation might persist for years if the infection is not resolved, resulting in harmful outcomes for the brain. We have previously demonstrated the efficacy of immunotherapy targeting the programmed cell death protein 1 (PD-1) pathway on clearance of Toxoplasma tissue cysts. We aimed to test whether parasite clearance would lead to the resolution of neuroinflammation in infected brains. We established chronic Toxoplasma infection in BALB/c mice using the cyst-forming Prugniaud strain. Mice then received αPD-L1 or isotype control antibodies. After completion of the therapy, mice were euthanized six weeks later. The number of brain tissue cysts, Toxoplasma-specific CD8 + T cell proliferation and IFN-γ secretion, serum cytokine and chemokine levels, and CNS inflammation were measured. In αPD-L1-treated mice, we observed reduced brain tissue cysts, increased spleen weight, elevated IFN-γ production by antigen-specific CD8 + T cells, and a general increase in multiple serum cytokines and chemokines. Importantly, αPD-L1-treated mice displayed attenuation of meningeal lymphocytes, reactive astrocytes, and C1q expression. The reduction in inflammation-related proteins is correlated with reduced parasite burden. These results suggest that promoting systemic immunity results in parasite clearance, which in turn alleviates neuroinflammation. Our study may have implications for some brain infections where neuroinflammation is a critical component. |
| first_indexed | 2024-04-10T19:43:05Z |
| format | Article |
| id | doaj.art-659c694dbe984e27861e7dac43328533 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T19:43:05Z |
| publishDate | 2023-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-659c694dbe984e27861e7dac433285332023-01-29T12:11:29ZengNature PortfolioScientific Reports2045-23222023-01-0113111210.1038/s41598-023-28322-8Immunotherapy targeting the PD-1 pathway alleviates neuroinflammation caused by chronic Toxoplasma infectionJianchun Xiao0Ye Li1Treva Rowley2Jing Huang3Robert H. Yolken4Raphael P. Viscidi5Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of MedicineStanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of MedicineDepartment of Pediatrics, Johns Hopkins School of MedicineStanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of MedicineStanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of MedicineDepartment of Pediatrics, Johns Hopkins School of MedicineAbstract Toxoplasma gondii can infect the host brain and trigger neuroinflammation. Such neuroinflammation might persist for years if the infection is not resolved, resulting in harmful outcomes for the brain. We have previously demonstrated the efficacy of immunotherapy targeting the programmed cell death protein 1 (PD-1) pathway on clearance of Toxoplasma tissue cysts. We aimed to test whether parasite clearance would lead to the resolution of neuroinflammation in infected brains. We established chronic Toxoplasma infection in BALB/c mice using the cyst-forming Prugniaud strain. Mice then received αPD-L1 or isotype control antibodies. After completion of the therapy, mice were euthanized six weeks later. The number of brain tissue cysts, Toxoplasma-specific CD8 + T cell proliferation and IFN-γ secretion, serum cytokine and chemokine levels, and CNS inflammation were measured. In αPD-L1-treated mice, we observed reduced brain tissue cysts, increased spleen weight, elevated IFN-γ production by antigen-specific CD8 + T cells, and a general increase in multiple serum cytokines and chemokines. Importantly, αPD-L1-treated mice displayed attenuation of meningeal lymphocytes, reactive astrocytes, and C1q expression. The reduction in inflammation-related proteins is correlated with reduced parasite burden. These results suggest that promoting systemic immunity results in parasite clearance, which in turn alleviates neuroinflammation. Our study may have implications for some brain infections where neuroinflammation is a critical component.https://doi.org/10.1038/s41598-023-28322-8 |
| spellingShingle | Jianchun Xiao Ye Li Treva Rowley Jing Huang Robert H. Yolken Raphael P. Viscidi Immunotherapy targeting the PD-1 pathway alleviates neuroinflammation caused by chronic Toxoplasma infection Scientific Reports |
| title | Immunotherapy targeting the PD-1 pathway alleviates neuroinflammation caused by chronic Toxoplasma infection |
| title_full | Immunotherapy targeting the PD-1 pathway alleviates neuroinflammation caused by chronic Toxoplasma infection |
| title_fullStr | Immunotherapy targeting the PD-1 pathway alleviates neuroinflammation caused by chronic Toxoplasma infection |
| title_full_unstemmed | Immunotherapy targeting the PD-1 pathway alleviates neuroinflammation caused by chronic Toxoplasma infection |
| title_short | Immunotherapy targeting the PD-1 pathway alleviates neuroinflammation caused by chronic Toxoplasma infection |
| title_sort | immunotherapy targeting the pd 1 pathway alleviates neuroinflammation caused by chronic toxoplasma infection |
| url | https://doi.org/10.1038/s41598-023-28322-8 |
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