Early detection of cerebrovascular pathology and protective antiviral immunity by MRI

Abstract
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Abstract

Central nervous system (CNS) infections are a major cause of human morbidity and mortality worldwide. Even patients that survive CNS infections can have lasting neurological dysfunction resulting from immune and pathogen induced pathology. Developing approaches to noninvasively track pathology and immunity in the infected CNS is crucial for patient management and development of new therapeutics. Here, we develop novel MRI-based approaches to monitor virus-specific CD8+ T cells and their relationship to cerebrovascular pathology in the living brain. We studied a relevant murine model in which a neurotropic virus (vesicular stomatitis virus) was introduced intranasally and then entered the brain via olfactory sensory neurons - a route exploited by many pathogens in humans. Using T2*-weighted high-resolution MRI, we identified small cerebral microbleeds as an early form of pathology associated with viral entry into the brain. Mechanistically, these microbleeds occurred in the absence of peripheral immune cells and were associated with infection of vascular endothelial cells. We monitored the adaptive response to this infection by developing methods to iron label and track individual virus specific CD8+ T cells by MRI. Transferred antiviral T cells were detected in the brain within a day of infection and were able to reduce cerebral microbleeds. These data demonstrate the utility of MRI in detecting the earliest pathological events in the virally infected CNS as well as the therapeutic potential of antiviral T cells in mitigating this pathology.

Data availability

The source data of this study wilb be available in Dryad (https://doi.org/10.5061/dryad.79cnp5hwp)

The following data sets were generated

1. Liu L
2. Dodd S
3. Hunt R
4. Pothayee N
5. Atanasijevic T
6. Bouraoud N
7. Maric D
8. Moseman E
9. Gossa S
10. McGavern D
11. Koretsky A
(2021) Dataset for: Early detection of cerebrovascular pathology and protective antiviral immunity by MRI
Dryad Digital Repository, doi:10.5061/dryad.79cnp5hwp.

https://dx.doi.org/10.5061/dryad.79cnp5hwp

Article and author information

Author details

Li Liu

Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, Bethesda, United States

For correspondence
li.liu3@nih.gov

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2493-3086
Steve Dodd

Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Ryan D Hunt

Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Nikorn Pothayee

Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Tatjana Atanasijevic

Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Nadia Bouraoud

Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Dragan Maric

Flow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
E Ashley Moseman

Department of Immunology, Duke University School of Medicine, Durham, United States

Competing interests
The authors declare that no competing interests exist.
Selamawit Gossa

Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Dorian B McGavern

Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Alan P Koretsky

Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, Bethesda, United States

For correspondence
koretskya@ninds.nih.gov

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8085-4756

Funding

the National Institute of Health

Alan P Koretsky

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.