Toll-like receptor 2 confers partial neuroprotection during prion disease.
Neuroinflammation and neurodegeneration are common during prion infection, but the mechanisms that underlie these pathological features are not well understood. Several components of innate immunity, such as Toll-like receptor (TLR) 4 and Complement C1q, have been shown to influence prion disease. T...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0208559 |
| _version_ | 1818588931288989696 |
|---|---|
| author | James A Carroll Brent Race Katie Williams Bruce Chesebro |
| author_facet | James A Carroll Brent Race Katie Williams Bruce Chesebro |
| author_sort | James A Carroll |
| collection | DOAJ |
| description | Neuroinflammation and neurodegeneration are common during prion infection, but the mechanisms that underlie these pathological features are not well understood. Several components of innate immunity, such as Toll-like receptor (TLR) 4 and Complement C1q, have been shown to influence prion disease. To identify additional components of innate immunity that might impact prion disease within the central nervous system (CNS), we screened RNA from brains of pre-clinical and clinical 22L-infected mice for alterations in genes associated with innate immunity. Transcription of several genes encoding damage-associated molecular pattern (DAMP) proteins and receptors were increased in the brains of prion-infected mice. To investigate the role of some of these proteins in prion disease of the CNS, we infected mice deficient in DAMP receptor genes Tlr2, C3ar1, and C5ar1 with 22L scrapie. Elimination of TLR2 accelerated disease by a median of 10 days, while lack of C3aR1 or C5aR1 had no effect on disease tempo. Histopathologically, all knockout mouse strains tested were similar to infected control mice in gliosis, vacuolation, and PrPSc deposition. Analysis of proinflammatory markers in the brains of infected knockout mice indicated only a few alterations in gene expression suggesting that C5aR1 and TLR2 signaling did not act synergistically in the brains of prion-infected mice. These results indicate that signaling through TLR2 confers partial neuroprotection during prion infection. |
| first_indexed | 2024-12-16T09:32:35Z |
| format | Article |
| id | doaj.art-9c73cd3201ab40c2ad32d80732ee0bec |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T09:32:35Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9c73cd3201ab40c2ad32d80732ee0bec2022-12-21T22:36:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011312e020855910.1371/journal.pone.0208559Toll-like receptor 2 confers partial neuroprotection during prion disease.James A CarrollBrent RaceKatie WilliamsBruce ChesebroNeuroinflammation and neurodegeneration are common during prion infection, but the mechanisms that underlie these pathological features are not well understood. Several components of innate immunity, such as Toll-like receptor (TLR) 4 and Complement C1q, have been shown to influence prion disease. To identify additional components of innate immunity that might impact prion disease within the central nervous system (CNS), we screened RNA from brains of pre-clinical and clinical 22L-infected mice for alterations in genes associated with innate immunity. Transcription of several genes encoding damage-associated molecular pattern (DAMP) proteins and receptors were increased in the brains of prion-infected mice. To investigate the role of some of these proteins in prion disease of the CNS, we infected mice deficient in DAMP receptor genes Tlr2, C3ar1, and C5ar1 with 22L scrapie. Elimination of TLR2 accelerated disease by a median of 10 days, while lack of C3aR1 or C5aR1 had no effect on disease tempo. Histopathologically, all knockout mouse strains tested were similar to infected control mice in gliosis, vacuolation, and PrPSc deposition. Analysis of proinflammatory markers in the brains of infected knockout mice indicated only a few alterations in gene expression suggesting that C5aR1 and TLR2 signaling did not act synergistically in the brains of prion-infected mice. These results indicate that signaling through TLR2 confers partial neuroprotection during prion infection.https://doi.org/10.1371/journal.pone.0208559 |
| spellingShingle | James A Carroll Brent Race Katie Williams Bruce Chesebro Toll-like receptor 2 confers partial neuroprotection during prion disease. PLoS ONE |
| title | Toll-like receptor 2 confers partial neuroprotection during prion disease. |
| title_full | Toll-like receptor 2 confers partial neuroprotection during prion disease. |
| title_fullStr | Toll-like receptor 2 confers partial neuroprotection during prion disease. |
| title_full_unstemmed | Toll-like receptor 2 confers partial neuroprotection during prion disease. |
| title_short | Toll-like receptor 2 confers partial neuroprotection during prion disease. |
| title_sort | toll like receptor 2 confers partial neuroprotection during prion disease |
| url | https://doi.org/10.1371/journal.pone.0208559 |
| work_keys_str_mv | AT jamesacarroll tolllikereceptor2conferspartialneuroprotectionduringpriondisease AT brentrace tolllikereceptor2conferspartialneuroprotectionduringpriondisease AT katiewilliams tolllikereceptor2conferspartialneuroprotectionduringpriondisease AT brucechesebro tolllikereceptor2conferspartialneuroprotectionduringpriondisease |