Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions
Standard
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, Jahrgang 54, Nr. 7, 13.07.2021, S. 1594-1610.e11.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
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 -