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| Status |
Public on Jul 27, 2021 |
| Title |
Antimicrobial immunity impedes CNS vascular repair following brain injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Traumatic brain injuries (TBI) and cerebrovascular injuries are leading causes of disability and mortality worldwide. Systemic infections often accompany these disorders, which can impede recovery and significantly worsen outcomes. Remodeling of the central nervous system (CNS) after injury is essential for functional recovery and depends on temporally and spatially coordinated innate immune responses; however, the effect of systemic infections on this process is not well understood. Here, we demonstrate that a broad range of systemically introduced microbes and pathogen-associated molecular patterns interfered with immune-mediated meningeal vascular repair after TBI, with sequential infections promoting a prolonged state of disrepair. Mechanistically, we discovered that MDA5-dependent detection of a noncytopathic arenavirus encountered after TBI disrupted pro-angiogenic programming in recruited myeloid cells via local induction of type I interferon signaling. Systemic viral infection similarly promoted type I interferon-dependent impairment of restorative angiogenesis in the brain parenchyma after intracranial hemorrhage, leading to chronic blood brain barrier leakage, sustained interferon signaling, and a failure to restore cognitive-motor function. Our findings reveal an immunological mechanism by which systemic infections deviate reparative programming after CNS injury and offer a new therapeutic target to improve recovery and prevent states of prolonged neurological decline.
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| Overall design |
Bulk RNA-Seq profiling of the cerebral cortex from twelve different mice in total; including four uninjured mice (Ctrl), four naïve cerebrovascular injured mice (CVI) at day 20 post-injury relative to uninjured mice, and four cerebrovascular injured mice at day 20 post-injury relative to uninjured mice infected with lymphocytic choriomeningitis virus (CVI LCMV).
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| Contributor(s) |
Mastorakos P, Russo MV, Zhou T, Johnson KR, McGavern DB |
| Citation(s) |
34556874 |
| Submission date |
Apr 14, 2021 |
| Last update date |
Oct 26, 2021 |
| Contact name |
Kory R Johnson |
| E-mail(s) |
johnsonko@ninds.nih.gov
|
| Phone |
301-402-1956
|
| Organization name |
NINDS/NIH
|
| Department |
DIR IT & Bioinformatics
|
| Lab |
Bioinformatics Section
|
| Street address |
10/3B01, 9000 Rockville Pike
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA722016 |
| SRA |
SRP314865 |
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