Direct and indirect effects of Puumala hantavirus on platelet function

Schrottmaier, Waltraud C.; Schmuckenschlager, Anna; Thunberg, Therese; Wigren-Byström, Julia; Fors-Connolly, Anne-Marie; Assinger, Alice; Ahlm, Clas; Forsell, Mattias N.E.

doi:10.1016/j.thromres.2023.11.017

Cited by 3 publications

(2 citation statements)

References 71 publications

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“…However, the complex processes that determine the inflammatory response in the kidney involve different renal cell types, which represent target cells of hantaviral infection 46–48 . In addition, PUUV directly activates neutrophils in vitro 49 . Therefore, the crosstalk between cells of the glomerulus, tubular apparatus, and immune system needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil‐to‐lymphocyte ratio is elevated in acute hantavirus infection and correlates with markers of disease severity

Nusshag,

Gruber,

Zeier

et al. 2024

Journal of Medical Virology

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Pathogenic Eurasian hantaviruses cause hemorrhagic fever with renal syndrome (HFRS), which is characterized by acute kidney injury. The clinical course shows a broad range of severity and is influenced by direct and immune‐mediated effects. The neutrophil‐to‐lymphocyte ratio (NLR) is a marker of systemic inflammation and predicts severity and outcome in various diseases. Therefore, we examined the role of NLR in HFRS caused by hantavirus Puumala (PUUV) and its association with disease severity and kidney injury. We detected elevated NLR levels on admission (NLRadm: median 3.82, range 1.75−7.59), which increased during acute HFRS. Maximum NLR levels (NLRmax: median 4.19, range 1.75−13.16) were 2.38‐fold higher compared to the reference NLR level of 1.76 in the general population. NLR levels on admission correlate with markers of severity (length of hospital stay, serum creatinine) but not with other markers of severity (leukocytes, platelets, C‐reactive protein, lactate dehydrogenase, serum albumin, proteinuria). Interestingly, levels of nephrin, which is a specific marker of podocyte damage in kidney injury, are highest on admission and correlate with NLRmax, but not with NLRadm. Together, we observed a correlation between systemic inflammation and the severity of HFRS, but our results also revealed that podocyte damage precedes these inflammatory processes.

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Section: Discussionmentioning

confidence: 99%

Neutrophil‐to‐lymphocyte ratio is elevated in acute hantavirus infection and correlates with markers of disease severity

Nusshag,

Gruber,

Zeier

et al. 2024

Journal of Medical Virology

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“…This consumption can result from platelet aggregation due to increased blood coagulation or platelet sequestration through immobilization to various surfaces. Recently, platelet binding to PUUV-infected endothelial cells was observed, suggesting a potential mechanism of platelet loss during PUUV-HFRS ( 37 ). Moreover, our previous findings indicated a positive correlation between neutrophil activation and thrombocytopenia in acute PUUV-HFRS ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

Maturing neutrophils of lower density associate with thrombocytopenia in Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome

Cabrera,

Tietäväinen,

Jokiranta

et al. 2024

Front. Immunol.

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Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by strong neutrophil activation. Neutrophils are the most abundant immune cell type in the circulation and are specially equipped to rapidly respond to infections. They are more heterogenous than previously appreciated, with specific neutrophil subsets recently implicated in inflammation and immunosuppression. Furthermore, neutrophils can be divided based on their density to either low-density granulocytes (LDGs) or “normal density” polymorphonuclear cell (PMN) fractions. In the current study we aimed to identify and characterize the different neutrophil subsets in the circulation of PUUV-HFRS patients. PMNs exhibited an activation of antiviral pathways, while circulating LDGs were increased in frequency following acute PUUV-HFRS. Furthermore, cell surface marker expression analysis revealed that PUUV-associated LDGs are primarily immature and most likely reflect an increased neutrophil production from the bone marrow. Interestingly, both the frequency of LDGs and the presence of a “left shift” in blood associated with the extent of thrombocytopenia, one of the hallmarks of severe HFRS, suggesting that maturing neutrophils could play a role in disease pathogenesis. These results imply that elevated circulating LDGs might be a general finding in acute viral infections. However, in contrast to the COVID-19 associated LDGs described previously, the secretome of PUUV LDGs did not show significant immunosuppressive ability, which suggests inherent biological differences in the LDG responses that can be dependent on the causative virus or differing infection kinetics.

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Maturing neutrophils of lower density associate with thrombocytopenia in Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome

Cabrera,

Tietäväinen,

Jokiranta

et al. 2024

Preprint

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Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by strong neutrophil activation. Neutrophils are the most abundant immune cell type in the circulation and are specially equipped to rapidly respond to infections. They are more heterogenous than previously appreciated, with specific neutrophil subsets recently implicated in inflammation and immunosuppression. Furthermore, neutrophils can be divided based on their density to either low-density granulocytes (LDGs) or “normal density” polymorphonuclear cell (PMN) fractions. In the current study we aimed to identify and characterize the different neutrophil subsets in the circulation of PUUV-HFRS patients. PMNs exhibited an activation of antiviral pathways, while circulating LDGs were increased in frequency following acute PUUV-HFRS. Furthermore, cell surface marker expression analysis revealed that PUUV-associated LDGs are primarily immature and most likely reflect an increased neutrophil production from the bone marrow. Interestingly, both the frequency of LDGs and the presence of a “left shift” in blood associated with the extent of thrombocytopenia, one of the hallmarks of severe HFRS, suggesting that immature neutrophils could play a role in disease pathogenesis. These results imply that elevated circulating LDGs might be a general finding in acute viral infections. However, in contrast to the COVID-19 associated LDGs described previously, the secretome of PUUV LDGs did not show significant immunosuppressive ability, which suggests inherent biological differences in the LDG responses that can be dependent on the causative virus or differing infection kinetics.

show abstract

Direct and indirect effects of Puumala hantavirus on platelet function

Cited by 3 publications

References 71 publications

Neutrophil‐to‐lymphocyte ratio is elevated in acute hantavirus infection and correlates with markers of disease severity

Neutrophil‐to‐lymphocyte ratio is elevated in acute hantavirus infection and correlates with markers of disease severity

Maturing neutrophils of lower density associate with thrombocytopenia in Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome

Maturing neutrophils of lower density associate with thrombocytopenia in Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome

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