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Publications in Cell Host and Microbe by NOMIS researchers

Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19

NOMIS Researcher(s)

Published in

December 11, 2024

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes. Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice. Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury. Vaccination reduced but did not eliminate spike protein accumulation after infection in mice. Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.

Research field(s)
Molecular Biology, Virology, Immunology

DOI
10.1016/j.chom.2024.11.007

Inflammasome-microbiota interplay in host physiologies

NOMIS Researcher(s)

Published in

November 13, 2013

Host defense responses against microbes are most often thought of in terms of effectors of microbial destruction. However, recent evidence demonstrates that the more complex interactions between the microbiota and innate immune mechanisms, such as the inflammasome-mediated response, cannot be readily explained within just the traditional paradigms of microbial killing mechanisms. In this review, the concepts of both resistance and tolerance are applied to inflammasome-microbiota interactions, and the various physiological consequences of this interplay, including roles in inflammation, tissue repair, tumorigenesis, and metabolism, are discussed. © 2013 Elsevier Inc.

Research field(s)
Health Sciences, Clinical Medicine, Immunology

DOI
10.1016/j.chom.2013.10.013

Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors

NOMIS Researcher(s)

Published in

August 14, 2013

Upon activation by the ligands Gas6 and Protein S, Tyro3/Axl/Mer (TAM) receptor tyrosine kinases promote phagocytic clearance of apoptotic cells and downregulate immune responses initiated by Toll-like receptors and type I interferons (IFNs). Many enveloped viruses display the phospholipid phosphatidylserine on their membranes, through which they bind Gas6 and Protein S and engage TAM receptors. We find that ligand-coated viruses activate TAM receptors on dendritic cells (DCs), dampen type I IFN signaling, and thereby evade host immunity and promote infection. Upon virus challenge, TAM-deficient DCs display type I IFN responses that are elevated in comparison to wild-type cells. As a consequence, TAM-deficient DCs are relatively resistant to infection by flaviviruses and pseudotyped retroviruses, but infection can be restored with neutralizing type I IFN antibodies. Correspondingly, a TAM kinase inhibitor antagonizes the infection of wild-type DCs. Thus, TAM receptors are engaged by viruses in order to attenuate type I IFN signaling and represent potential therapeutic targets. © 2013 Elsevier Inc.

Research field(s)
Health Sciences, Clinical Medicine, Immunology

DOI
10.1016/j.chom.2013.07.005

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