Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19

Fekete Rebeka; Simats Alba; Bíró Eduárd; Pósfai Balázs; Cserép Csaba; Schwarcz Dóra Anett; Cserépné Szabadits Eszter; Környei Zsuzsanna; Tóth Krisztina; Fichó Erzsébet; Szalma János; Vida Sára; Kellermayer Anna; Dávid Csaba; Acsády László; Kontra Levente; Silvestre-Roig Carlos; Moldvay Judit; Fillinger János; Csikász-Nagy Attila; Hortobágyi Tibor; Liesz Arthur; Benkő Szilvia; Dénes Ádám: Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19.
NATURE NEUROSCIENCE, 28 (3). pp. 558-576. ISSN 1097-6256 (2025)

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Folyóiratcikk

Szerző azonosítók:

Név	ORCID	MTMT szerző azonosító
Fekete Rebeka		10049451
Simats Alba
Bíró Eduárd		10078021
Pósfai Balázs	0000-0003-1035-565X	10061174
Cserép Csaba	0000-0001-5513-2471	172
Schwarcz Dóra Anett		10063826
Cserépné Szabadits Eszter		173
Környei Zsuzsanna		10011503
Tóth Krisztina		10064506
Fichó Erzsébet	0000-0002-3965-8438	10061311
Szalma János	0000-0003-4167-1858	10091234
Vida Sára	0009-0009-9566-614X	10104526
Kellermayer Anna		10085407
Dávid Csaba		10018448
Acsády László		10009548
Kontra Levente		10057362
Silvestre-Roig Carlos
Moldvay Judit		10003072
Fillinger János		10023823
Csikász-Nagy Attila	0000-0002-2919-5601	10012379
Hortobágyi Tibor	0000-0001-5732-7942	10017334
Liesz Arthur	0000-0002-9069-2594
Benkő Szilvia		10020759
Dénes Ádám		10012934

Absztrakt (kivonat):

COVID-19 is associated with diverse neurological abnormalities, but the underlying mechanisms are unclear. We hypothesized that microglia, the resident immune cells of the brain, are centrally involved in this process. To study this, we developed an autopsy platform allowing the integration of molecular anatomy, protein and mRNA datasets in postmortem mirror blocks of brain and peripheral organ samples from cases of COVID-19. We observed focal loss of microglial P2Y12R, CX3CR1–CX3CL1 axis deficits and metabolic failure at sites of virus-associated vascular inflammation in severely affected medullary autonomic nuclei and other brain areas. Microglial dysfunction is linked to mitochondrial injury at sites of excessive synapse and myelin phagocytosis and loss of glutamatergic terminals, in line with proteomic changes of synapse assembly, metabolism and neuronal injury. Furthermore, regionally heterogeneous microglial changes are associated with viral load and central and systemic inflammation related to interleukin (IL)-1 or IL-6 via virus-sensing pattern recognition receptors and inflammasomes. Thus, SARS-CoV-2-induced inflammation might lead to a primarily gliovascular failure in the brain, which could be a common contributor to diverse COVID-19-related neuropathologies.

Folyóirat címe:

NATURE NEUROSCIENCE

Megjelenés éve:

2025

Kötet:

Szám:

Oldalak:

pp. 558-576

ISSN:

1097-6256

Intézmény:

Pázmány Péter Katolikus Egyetem