CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination.
Neurotropic mouse hepatitis virus (MHV-A59/RSA59) infection in mice induces acute neuroinflammation due to direct neural cell dystrophy, which proceeds with demyelination with or without axonal loss, the pathological hallmarks of human neurological disease, Multiple sclerosis (MS). Recent studies in...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010059&type=printable |
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| author | Fareeha Saadi Debanjana Chakravarty Saurav Kumar Mithila Kamble Bhaskar Saha Kenneth S Shindler Jayasri Das Sarma |
| author_facet | Fareeha Saadi Debanjana Chakravarty Saurav Kumar Mithila Kamble Bhaskar Saha Kenneth S Shindler Jayasri Das Sarma |
| author_sort | Fareeha Saadi |
| collection | DOAJ |
| description | Neurotropic mouse hepatitis virus (MHV-A59/RSA59) infection in mice induces acute neuroinflammation due to direct neural cell dystrophy, which proceeds with demyelination with or without axonal loss, the pathological hallmarks of human neurological disease, Multiple sclerosis (MS). Recent studies in the RSA59-induced neuroinflammation model of MS showed a protective role of CNS-infiltrating CD4+ T cells compared to their pathogenic role in the autoimmune model. The current study further investigated the molecular nexus between CD4+ T cell-expressed CD40Ligand and microglia/macrophage-expressed CD40 using CD40L-/- mice. Results demonstrate CD40L expression in the CNS is modulated upon RSA59 infection. We show evidence that CD40L-/- mice are more susceptible to RSA59 induced disease due to reduced microglia/macrophage activation and significantly dampened effector CD4+ T recruitment to the CNS on day 10 p.i. Additionally, CD40L-/- mice exhibited severe demyelination mediated by phagocytic microglia/macrophages, axonal loss, and persistent poliomyelitis during chronic infection, indicating CD40-CD40L as host-protective against RSA59-induced demyelination. This suggests a novel target in designing prophylaxis for virus-induced demyelination and axonal degeneration, in contrast to immunosuppression which holds only for autoimmune mechanisms of inflammatory demyelination. |
| format | Article |
| id | doaj-art-0d32a0937bd4438eb7f5817beeb6e725 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-0d32a0937bd4438eb7f5817beeb6e7252025-08-20T02:17:47ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-12-011712e101005910.1371/journal.ppat.1010059CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination.Fareeha SaadiDebanjana ChakravartySaurav KumarMithila KambleBhaskar SahaKenneth S ShindlerJayasri Das SarmaNeurotropic mouse hepatitis virus (MHV-A59/RSA59) infection in mice induces acute neuroinflammation due to direct neural cell dystrophy, which proceeds with demyelination with or without axonal loss, the pathological hallmarks of human neurological disease, Multiple sclerosis (MS). Recent studies in the RSA59-induced neuroinflammation model of MS showed a protective role of CNS-infiltrating CD4+ T cells compared to their pathogenic role in the autoimmune model. The current study further investigated the molecular nexus between CD4+ T cell-expressed CD40Ligand and microglia/macrophage-expressed CD40 using CD40L-/- mice. Results demonstrate CD40L expression in the CNS is modulated upon RSA59 infection. We show evidence that CD40L-/- mice are more susceptible to RSA59 induced disease due to reduced microglia/macrophage activation and significantly dampened effector CD4+ T recruitment to the CNS on day 10 p.i. Additionally, CD40L-/- mice exhibited severe demyelination mediated by phagocytic microglia/macrophages, axonal loss, and persistent poliomyelitis during chronic infection, indicating CD40-CD40L as host-protective against RSA59-induced demyelination. This suggests a novel target in designing prophylaxis for virus-induced demyelination and axonal degeneration, in contrast to immunosuppression which holds only for autoimmune mechanisms of inflammatory demyelination.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010059&type=printable |
| spellingShingle | Fareeha Saadi Debanjana Chakravarty Saurav Kumar Mithila Kamble Bhaskar Saha Kenneth S Shindler Jayasri Das Sarma CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination. PLoS Pathogens |
| title | CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination. |
| title_full | CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination. |
| title_fullStr | CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination. |
| title_full_unstemmed | CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination. |
| title_short | CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination. |
| title_sort | cd40l protects against mouse hepatitis virus induced neuroinflammatory demyelination |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010059&type=printable |
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