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Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling.

ABSTRACT: Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as β-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher β-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

SUBMITTER: Giron LB

PROVIDER: S-EPMC9462470 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling.

Giron Leila B LB Peluso Michael J MJ Ding Jianyi J Kenny Grace G Zilberstein Netanel F NF Koshy Jane J Hong Kai Ying KY Rasmussen Heather H Miller Gregory E GE Bishehsari Faraz F Balk Robert A RA Moy James N JN Hoh Rebecca R Lu Scott S Goldman Aaron R AR Tang Hsin-Yao HY Yee Brandon C BC Chenna Ahmed A Winslow John W JW Petropoulos Christos J CJ Kelly J Daniel JD Wasse Haimanot H Martin Jeffrey N JN Liu Qin Q Keshavarzian Ali A Landay Alan A Deeks Steven G SG Henrich Timothy J TJ Abdel-Mohsen Mohamed M

JCI insight 20220808 15

Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma mark ...[more]

PMID: 35727635

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Dataset Information

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling.

Publications

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling.

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