Antimicrobial immunity impedes CNS vascular repair following brain injury.
Panagiotis MastorakosMatthew V RussoTianzan ZhouKory JohnsonDorian B McGavernPublished in: Nature immunology (2021)
Traumatic brain injury (TBI) and cerebrovascular injury are leading causes of disability and mortality worldwide. Systemic infections often accompany these disorders and can worsen outcomes. Recovery after brain injury depends on innate immunity, but the effect of infections on this process is not well understood. Here, we demonstrate that systemically introduced microorganisms and microbial products interfered with meningeal vascular repair after TBI in a type I interferon (IFN-I)-dependent manner, with sequential infections promoting chronic disrepair. Mechanistically, we discovered that MDA5-dependent detection of an arenavirus encountered after TBI disrupted pro-angiogenic myeloid cell programming via induction of IFN-I signaling. Systemic viral infection similarly blocked restorative angiogenesis in the brain parenchyma after intracranial hemorrhage, leading to chronic IFN-I signaling, blood-brain barrier leakage and a failure to restore cognitive-motor function. Our findings reveal a common immunological mechanism by which systemic infections deviate reparative programming after central nervous system injury and offer a new therapeutic target to improve recovery.
Keyphrases
- brain injury
- traumatic brain injury
- blood brain barrier
- cerebral ischemia
- subarachnoid hemorrhage
- dendritic cells
- immune response
- severe traumatic brain injury
- single cell
- multiple sclerosis
- resting state
- bone marrow
- mild traumatic brain injury
- cardiovascular disease
- risk factors
- microbial community
- staphylococcus aureus
- vascular endothelial growth factor
- drug induced
- acute myeloid leukemia
- white matter
- endothelial cells
- genome wide
- cerebrospinal fluid
- functional connectivity
- signaling pathway
- breast cancer cells
- pi k akt
- cell cycle arrest
- wound healing