Maturing Neutrophils of Lower Density Associate with Thrombocytopenia in Puumala Orthohantavirus-Caused Hemorrhagic Fever with Renal Syndrome - Human samples
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1127560 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29526500.fastq.gz | Fastqsanger.gz | |||
| SRR29526600.fastq.gz | Fastqsanger.gz | |||
| SRR29526501.fastq.gz | Fastqsanger.gz | |||
| SRR29526601.fastq.gz | Fastqsanger.gz | |||
| SRR29526502.fastq.gz | Fastqsanger.gz |
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Project description:Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by significant neutrophil activation. Neutrophils, the most abundant immune cells in circulation, are equipped to respond rapidly to infections and exhibit a notable heterogeneity. This study aims to identify and characterize different neutrophil subsets in the circulation of PUUV-HFRS patients, focusing on low-density granulocytes (LDGs) and normal density polymorphonuclear cells (PMNs). The study finds that PMNs show activation of antiviral pathways, while circulating LDGs increase following acute PUUV-HFRS. Additionally, PUUV-associated LDGs, primarily immature, likely reflect increased bone marrow neutrophil production. Notably, the frequency of LDGs and a "left shift" in blood are associated with the extent of thrombocytopenia, a hallmark of severe HFRS, suggesting a role for maturing neutrophils in disease pathogenesis. Unlike COVID-19 associated LDGs, PUUV LDGs did not exhibit significant immunosuppressive ability, indicating inherent biological differences in LDG responses based on the causative virus or infection kinetics. RNA sequencing was performed on neutrophils isolated from four cohorts: healthy control PMNs, PUUV-infected PMNs, PUUV-infected CD16- LDGs, and PUUV-infected CD16+ LDGs. The RNA sequencing and subsequent bioinformatics analysis were conducted by the Biomedicum Functional Genomics Unit at the Helsinki Institute of Life Science and Biocenter Finland at the University of Helsinki.
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Project description: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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