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J Infect . CD151 identifies a NK cell subset that is enriched in COVID-19 patients and correlates with disease severity

tetano

Editor, Senior Moderator
J Infect


. 2024 Oct 5:106304.
doi: 10.1016/j.jinf.2024.106304. Online ahead of print. CD151 identifies a NK cell subset that is enriched in COVID-19 patients and correlates with disease severity

Ainhoa Amarilla-Irusta[SUP] 1 [/SUP], Olatz Zenarruzabeitia[SUP] 2 [/SUP], Arrate Sevilla[SUP] 1 [/SUP], Víctor Sandá[SUP] 1 [/SUP], Ainara Lopez-Pardo[SUP] 1 [/SUP], Gabirel Astarloa-Pando[SUP] 1 [/SUP], Raquel Pérez-Garay[SUP] 3 [/SUP], Silvia Pérez-Fernández[SUP] 4 [/SUP], Susana Meijide[SUP] 4 [/SUP], Natale Imaz-Ayo[SUP] 4 [/SUP], Eunate Arana-Arri[SUP] 4 [/SUP], Laura Amo[SUP] 5 [/SUP], Francisco Borrego[SUP] 6 [/SUP]



Affiliations
Abstract

Severe coronavirus disease 2019 (COVID-19) often lead to acute respiratory distress syndrome and multi-organ dysfunction, driven by a dysregulated immune response, including a cytokine storm with elevated proinflammatory cytokine levels. Natural killer (NK) cells are part of the innate immune system with a fundamental role in the defense against viral infections. However, during COVID-19 acute infection, they exhibit an altered phenotype and impaired functionality contributing to the immunopathogenesis of the disease. In this work, we have studied a cohort of patients with COVID-19 (ranging from mild to severe) by analyzing IL-15, TGF-β, PlGF and GDF-15 plasma levels and performing multiparametric flow cytometry studies. Our results revealed that severe COVID-19 patients exhibited high levels of IL-15, PlGF and GDF-15, along with an enrichment of a NK cell subset expressing the CD151 tetraspanin, which correlated with IL-15 plasma levels and disease severity. In patients, these CD151+ NK cells displayed a more activated phenotype characterized by an increased expression of HLA-DR, CD38 and granzyme B, a distinct receptor repertoire, with lower levels of CD160 and CD31 and higher levels of CD55 and, remarkably, a higher expression of tissue-resident markers CD103 and the NK cell decidual marker CD9. Last of all, in individuals with severe disease, we identified an expansion of a CD151[SUP]bright[/SUP]CD9+ NK cell subset, suggesting that these cells play a specific role in COVID-19. Altogether, our findings suggest that CD151+ NK cells may have a relevant role in COVID-19 immunopathogenesis.

Keywords: CD151; CD9; COVID-19; GDF-15; IL-15; NK cells; SARS-CoV-2; TGF-β.

 
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