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Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

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Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions. / Schwabenland, Marius; Salié, Henrike; Tanevski, Jovan; Killmer, Saskia; Lago, Marilyn Salvat; Schlaak, Alexandra Emilia; Mayer, Lena; Matschke, Jakob; Püschel, Klaus; Fitzek, Antonia; Ondruschka, Benjamin; Mei, Henrik E; Boettler, Tobias; Neumann-Haefelin, Christoph; Hofmann, Maike; Breithaupt, Angele; Genc, Nafiye; Stadelmann, Christine; Saez-Rodriguez, Julio; Bronsert, Peter; Knobeloch, Klaus-Peter; Blank, Thomas; Thimme, Robert; Glatzel, Markus; Prinz, Marco; Bengsch, Bertram.

In: IMMUNITY, Vol. 54, No. 7, 13.07.2021, p. 1594-1610.e11.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schwabenland, M, Salié, H, Tanevski, J, Killmer, S, Lago, MS, Schlaak, AE, Mayer, L, Matschke, J, Püschel, K, Fitzek, A, Ondruschka, B, Mei, HE, Boettler, T, Neumann-Haefelin, C, Hofmann, M, Breithaupt, A, Genc, N, Stadelmann, C, Saez-Rodriguez, J, Bronsert, P, Knobeloch, K-P, Blank, T, Thimme, R, Glatzel, M, Prinz, M & Bengsch, B 2021, 'Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions', IMMUNITY, vol. 54, no. 7, pp. 1594-1610.e11. https://doi.org/10.1016/j.immuni.2021.06.002

APA

Schwabenland, M., Salié, H., Tanevski, J., Killmer, S., Lago, M. S., Schlaak, A. E., Mayer, L., Matschke, J., Püschel, K., Fitzek, A., Ondruschka, B., Mei, H. E., Boettler, T., Neumann-Haefelin, C., Hofmann, M., Breithaupt, A., Genc, N., Stadelmann, C., Saez-Rodriguez, J., ... Bengsch, B. (2021). Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions. IMMUNITY, 54(7), 1594-1610.e11. https://doi.org/10.1016/j.immuni.2021.06.002

Vancouver

Schwabenland M, Salié H, Tanevski J, Killmer S, Lago MS, Schlaak AE et al. Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions. IMMUNITY. 2021 Jul 13;54(7):1594-1610.e11. https://doi.org/10.1016/j.immuni.2021.06.002

Bibtex

@article{2ba4f4ec0ff640b8b37e9ed3d32ac0cc,
title = "Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions",
abstract = "COVID-19 can cause severe neurological symptoms, but the underlying pathophysiological mechanisms are unclear. Here, we interrogated the brain stems and olfactory bulbs in postmortem patients who had COVID-19 using imaging mass cytometry to understand the local immune response at a spatially resolved, high-dimensional, single-cell level and compared their immune map to non-COVID respiratory failure, multiple sclerosis, and control patients. We observed substantial immune activation in the central nervous system with pronounced neuropathology (astrocytosis, axonal damage, and blood-brain-barrier leakage) and detected viral antigen in ACE2-receptor-positive cells enriched in the vascular compartment. Microglial nodules and the perivascular compartment represented COVID-19-specific, microanatomic-immune niches with context-specific cellular interactions enriched for activated CD8+ T cells. Altered brain T-cell-microglial interactions were linked to clinical measures of systemic inflammation and disturbed hemostasis. This study identifies profound neuroinflammation with activation of innate and adaptive immune cells as correlates of COVID-19 neuropathology, with implications for potential therapeutic strategies.",
keywords = "Blood-Brain Barrier/immunology, Brain/immunology, CD8-Positive T-Lymphocytes/immunology, COVID-19/immunology, Cell Communication, Central Nervous System/immunology, Humans, Immune Checkpoint Proteins/metabolism, Inflammation, Lymphocyte Activation, Microglia/immunology, Multiple Sclerosis/immunology, Olfactory Bulb/immunology, Respiratory Insufficiency/immunology, SARS-CoV-2, Spike Glycoprotein, Coronavirus/metabolism, T-Lymphocyte Subsets/immunology",
author = "Marius Schwabenland and Henrike Sali{\'e} and Jovan Tanevski and Saskia Killmer and Lago, {Marilyn Salvat} and Schlaak, {Alexandra Emilia} and Lena Mayer and Jakob Matschke and Klaus P{\"u}schel and Antonia Fitzek and Benjamin Ondruschka and Mei, {Henrik E} and Tobias Boettler and Christoph Neumann-Haefelin and Maike Hofmann and Angele Breithaupt and Nafiye Genc and Christine Stadelmann and Julio Saez-Rodriguez and Peter Bronsert and Klaus-Peter Knobeloch and Thomas Blank and Robert Thimme and Markus Glatzel and Marco Prinz and Bertram Bengsch",
note = "Copyright {\textcopyright} 2021 Elsevier Inc. All rights reserved.",
year = "2021",
month = jul,
day = "13",
doi = "10.1016/j.immuni.2021.06.002",
language = "English",
volume = "54",
pages = "1594--1610.e11",
journal = "IMMUNITY",
issn = "1074-7613",
publisher = "Cell Press",
number = "7",

}

RIS

TY - JOUR

T1 - Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

AU - Schwabenland, Marius

AU - Salié, Henrike

AU - Tanevski, Jovan

AU - Killmer, Saskia

AU - Lago, Marilyn Salvat

AU - Schlaak, Alexandra Emilia

AU - Mayer, Lena

AU - Matschke, Jakob

AU - Püschel, Klaus

AU - Fitzek, Antonia

AU - Ondruschka, Benjamin

AU - Mei, Henrik E

AU - Boettler, Tobias

AU - Neumann-Haefelin, Christoph

AU - Hofmann, Maike

AU - Breithaupt, Angele

AU - Genc, Nafiye

AU - Stadelmann, Christine

AU - Saez-Rodriguez, Julio

AU - Bronsert, Peter

AU - Knobeloch, Klaus-Peter

AU - Blank, Thomas

AU - Thimme, Robert

AU - Glatzel, Markus

AU - Prinz, Marco

AU - Bengsch, Bertram

N1 - Copyright © 2021 Elsevier Inc. All rights reserved.

PY - 2021/7/13

Y1 - 2021/7/13

N2 - COVID-19 can cause severe neurological symptoms, but the underlying pathophysiological mechanisms are unclear. Here, we interrogated the brain stems and olfactory bulbs in postmortem patients who had COVID-19 using imaging mass cytometry to understand the local immune response at a spatially resolved, high-dimensional, single-cell level and compared their immune map to non-COVID respiratory failure, multiple sclerosis, and control patients. We observed substantial immune activation in the central nervous system with pronounced neuropathology (astrocytosis, axonal damage, and blood-brain-barrier leakage) and detected viral antigen in ACE2-receptor-positive cells enriched in the vascular compartment. Microglial nodules and the perivascular compartment represented COVID-19-specific, microanatomic-immune niches with context-specific cellular interactions enriched for activated CD8+ T cells. Altered brain T-cell-microglial interactions were linked to clinical measures of systemic inflammation and disturbed hemostasis. This study identifies profound neuroinflammation with activation of innate and adaptive immune cells as correlates of COVID-19 neuropathology, with implications for potential therapeutic strategies.

AB - COVID-19 can cause severe neurological symptoms, but the underlying pathophysiological mechanisms are unclear. Here, we interrogated the brain stems and olfactory bulbs in postmortem patients who had COVID-19 using imaging mass cytometry to understand the local immune response at a spatially resolved, high-dimensional, single-cell level and compared their immune map to non-COVID respiratory failure, multiple sclerosis, and control patients. We observed substantial immune activation in the central nervous system with pronounced neuropathology (astrocytosis, axonal damage, and blood-brain-barrier leakage) and detected viral antigen in ACE2-receptor-positive cells enriched in the vascular compartment. Microglial nodules and the perivascular compartment represented COVID-19-specific, microanatomic-immune niches with context-specific cellular interactions enriched for activated CD8+ T cells. Altered brain T-cell-microglial interactions were linked to clinical measures of systemic inflammation and disturbed hemostasis. This study identifies profound neuroinflammation with activation of innate and adaptive immune cells as correlates of COVID-19 neuropathology, with implications for potential therapeutic strategies.

KW - Blood-Brain Barrier/immunology

KW - Brain/immunology

KW - CD8-Positive T-Lymphocytes/immunology

KW - COVID-19/immunology

KW - Cell Communication

KW - Central Nervous System/immunology

KW - Humans

KW - Immune Checkpoint Proteins/metabolism

KW - Inflammation

KW - Lymphocyte Activation

KW - Microglia/immunology

KW - Multiple Sclerosis/immunology

KW - Olfactory Bulb/immunology

KW - Respiratory Insufficiency/immunology

KW - SARS-CoV-2

KW - Spike Glycoprotein, Coronavirus/metabolism

KW - T-Lymphocyte Subsets/immunology

U2 - 10.1016/j.immuni.2021.06.002

DO - 10.1016/j.immuni.2021.06.002

M3 - SCORING: Journal article

C2 - 34174183

VL - 54

SP - 1594-1610.e11

JO - IMMUNITY

JF - IMMUNITY

SN - 1074-7613

IS - 7

ER -