Sci Transl Med . SARS-CoV-2 induces neutrophil degranulation and differentiation into myeloid-derived suppressor cells associated with severe COVID

[tetano]

Sci Transl Med


. 2025 May 21;17(799):eadn7527.
doi: 10.1126/scitranslmed.adn7527. Epub 2025 May 21. SARS-CoV-2 induces neutrophil degranulation and differentiation into myeloid-derived suppressor cells associated with severe COVID-19

Leon L Hsieh[SUP] 1 2 [/SUP], Elizabeth A Thompson[SUP] 2 [/SUP], Nirvani P Jairam[SUP] 1 [/SUP], Katerina Roznik[SUP] 1 2 [/SUP], Alexis Figueroa[SUP] 1 [/SUP], Tihitina Aytenfisu[SUP] 1 [/SUP], Weiqiang Zhou[SUP] 3 [/SUP], Naina Gour[SUP] 4 [/SUP], Kuan-Hao Chao[SUP] 5 [/SUP], Aaron M Milstone[SUP] 6 [/SUP], Emily Egbert[SUP] 6 [/SUP], Franco D'Alessio[SUP] 1 [/SUP], Petros C Karakousis[SUP] 1 2 7 [/SUP], Alvaro Ordoñez[SUP] 6 [/SUP], Eileen P Scully[SUP] 1 [/SUP], Andrew Pekosz[SUP] 2 [/SUP], Andrew H Karaba[SUP] 1 [/SUP], Andrea L Cox[SUP] 1 2 8 [/SUP]



Affiliations

• PMID: 40397714
• DOI: 10.1126/scitranslmed.adn7527

Abstract

Severe COVID-19 presents with a distinct immunological profile, characterized by elevated neutrophil and reduced lymphocyte counts, seen commonly in fungal and bacterial infections. This study demonstrates that patients hospitalized with COVID-19 show evidence of neutrophil degranulation and have increased expression of neutrophil surface lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a marker of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Both early LOX-1 and programmed death-ligand 1 (PD-L1) expression on neutrophils were associated with development of severe disease. To determine whether tissue damage or inflammation is required to induce PMN-MDSCs or whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly activates neutrophils to become PMN-MDSCs, we incubated healthy human neutrophils with SARS-CoV-2. SARS-CoV-2 rapidly induced LOX-1 surface expression in healthy neutrophils independent of productive infection. LOX-1 induction was dependent on granule exocytosis and promoted up-regulation of reactive oxygen species, CD63, and PD-L1, enabling LOX-1[SUP]+[/SUP] neutrophils to suppress autologous T cell proliferation in vitro. These results support a role for PMN-MDSCs in mediating severe COVID-19, and inhibition of PD-L1 represents a potential therapeutic strategy for enhancing the immune response in acute SARS-CoV-2 infection.


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[sharon sanders]

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Health
23 May 2025 12:40 am AEST
Share Research: COVID Virus Turns Fighters Into Suppressors

Johns Hopkins Medicine A National Institutes of Health (NIH)-funded study by researchers from Johns Hopkins Medicine, the Johns Hopkins Bloomberg School of Public Health and The Johns Hopkins University Whiting School of Engineering finds that neutrophils - the most abundant type of white blood cells in humans - may be altered by SARS-CoV-2, the virus that causes COVID-19, to cease their normal function of destroying pathogens in the body and, instead, significantly inhibit other immune cells critical for fighting the virus.

The study was posted late yesterday in the journal Science Translational Medicine.

"Our findings suggest that in some COVID infections, SARS-CoV-2 may dramatically impair the immune response by reprogramming neutrophils - front-line immune cells central to fighting infections - into a cell type called polymorphonuclear myeloid derived suppressor cells, or PMN-MDSCs," says study senior author Andrea Cox, M.D., Ph.D., professor of medicine and oncology at the Johns Hopkins University School of Medicine. "PMN-MDSCs are known to suppress virus-fighting immune cells known as T lymphocytes, or T cells, and we believe the reprogramming that creates them could provide a mechanism by which severe COVID, a more dangerous form of the disease, may arise."​

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Hsieh says the researchers also co-cultured neutrophils with H1N1 influenza virus, but did not see any conversion to PMN-MDSCs. Additionally, an earlier study reported that PMN-MDSCs were not found in people hospitalized with severe influenza infections.

"So, it appears that not all viruses can cause the differentiation," Hsieh says.

Cox says the team's findings suggest that SARS-CoV-2 may directly induce neutrophils to take on the functions of a PMN-MDSC, and in turn, weaken the immune response against the virus enough to cause severe COVID.
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more....https://www.miragenews.com/research-covid-virus-turns-fighters-into-1465174/