Advances and Challenges in Sepsis Management: Modern Tools and Future Directions DOI Creative Commons
Elena Santacroce,

Miriam D’Angerio,

Alin Liviu Ciobanu

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 439 - 439

Published: March 2, 2024

Sepsis, a critical condition marked by systemic inflammation, profoundly impacts both innate and adaptive immunity, often resulting in lymphopenia. This immune alteration can spare regulatory T cells (Tregs) but significantly affects other lymphocyte subsets, leading to diminished effector functions, altered cytokine profiles, metabolic changes. The complexity of sepsis stems not only from its pathophysiology also the heterogeneity patient responses, posing significant challenges developing universally effective therapies. review emphasizes importance phenotyping enhance patient-specific diagnostic therapeutic strategies. Phenotyping cells, which categorizes patients based on clinical immunological characteristics, is pivotal for tailoring treatment approaches. Flow cytometry emerges as crucial tool this endeavor, offering rapid, low cost detailed analysis cell populations their functional states. Indeed, technology facilitates understanding dysfunctions contributes identification novel biomarkers. Our underscores potential integrating flow with omics data, machine learning observations refine management, highlighting shift towards personalized medicine care. approach could lead more precise interventions, improving outcomes heterogeneously affected population.

Language: Английский

Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19 DOI Creative Commons
Can Liu, Andrew J. Martins, William Lau

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(7), P. 1836 - 1857.e22

Published: Feb. 10, 2021

Language: Английский

Citations

209
Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells DOI Creative Commons
Mario Witkowski, Caroline Tizian, Marta Ferreira‐Gomes

et al.

Nature, Journal Year: 2021, Volume and Issue: 600(7888), P. 295 - 301

Published: Oct. 25, 2021

Language: Английский

Citations

202
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19 DOI Creative Commons
Benjamin Krämer, Rainer Knoll, Lorenzo Bonaguro

et al.

Immunity, Journal Year: 2021, Volume and Issue: 54(11), P. 2650 - 2669.e14

Published: Sept. 4, 2021

Language: Английский

Citations

194
MAIT cell activation and dynamics associated with COVID-19 disease severity DOI Creative Commons
Tiphaine Parrot, Jean‐Baptiste Gorin, Andrea Ponzetta

et al.

Science Immunology, Journal Year: 2020, Volume and Issue: 5(51)

Published: Sept. 18, 2020

MAIT cell activation and decline in blood are associated with COVID-19 severity, features that dynamically recover convalescence.

Language: Английский

Citations

186
Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19 DOI Creative Commons
Aaron J. Wilk, Madeline Lee, Bei Wei

et al.

The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(8)

Published: June 15, 2021

Our understanding of protective versus pathological immune responses to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is limited by inadequate profiling patients at extremes severity spectrum. Here, we performed multi-omic single-cell 64 COVID-19 across full range severity, from outpatients with mild fatal cases. transcriptomic, epigenomic, and proteomic analyses revealed widespread dysfunction peripheral innate immunity in severe COVID-19, including prominent hyperactivation signatures neutrophils NK cells. We also identified chromatin accessibility changes NF-κB binding sites within cytokine gene loci as a potential mechanism for striking lack pro-inflammatory production observed monocytes COVID-19. further demonstrated emergency myelopoiesis feature Collectively, our results reveal severity-associated phenotypes identify pathogenesis-associated pathways are targets therapeutic intervention.

Language: Английский

Citations

184
Innate immunological pathways in COVID-19 pathogenesis DOI
Søren R. Paludan, Trine H. Mogensen

Science Immunology, Journal Year: 2022, Volume and Issue: 7(67)

Published: Jan. 7, 2022

Coronavirus disease 2019 (COVID-19) is a characterized by profound dysregulation of the innate immune system. This knowledge has emerged from large body single-cell omics studies patients with COVID-19, which have provided one most detailed cellular atlases human ever. However, we are only beginning to understand immunological pathways that govern host defense and immunopathology in COVID-19. In this review, discuss emerging understanding how SARS-CoV-2 host-derived molecules activate specific pattern recognition receptors elicit protective interferon responses pathological cytokine responses, particular focus on acute infection lung pathophysiology critical addition, these modulated virus-host interactions stress-sensing pathways. In-depth mechanisms will likely uncover molecular targets for treatment COVID-19 other viral infections. it reveal fine balance between beneficial versus causing responses.

Language: Английский

Citations

164
Immunity to SARS‐CoV‐2 induced by infection or vaccination DOI Creative Commons
Xaquín Castro Dopico, Sebastian Ols, Karin Loré

et al.

Journal of Internal Medicine, Journal Year: 2021, Volume and Issue: 291(1), P. 32 - 50

Published: Aug. 5, 2021

Abstract Adaptive immune responses play critical roles in viral clearance and protection against re‐infection, SARS‐CoV‐2 is no exception. What exceptional the rapid characterization of response to virus performed by researchers during first 20 months pandemic. This has given us a more detailed understanding compared many viruses that have been with for long time. Furthermore, effective COVID‐19 vaccines were developed record time, their rollout worldwide already making significant difference, although major challenges remain terms equal access. The pandemic engaged scientists public alike, such as seroprevalence , neutralizing antibodies antibody escape vaccine certificates become familiar broad community. Here, we review key findings concerning B cell (Ab) SARS‐CoV‐2, focusing on non‐severe cases anti‐spike (S) Ab particular, latter being central protective immunity induced infection or vaccination. emergence variants acquired mutations S acutely highlights need continued both emerging these evolving pathogen‐immune system arms race.

Language: Английский

Citations

156
Human NK cells, their receptors and function DOI
Linda Quatrini,

Mariella Della Chiesa,

Simona Sivori

et al.

European Journal of Immunology, Journal Year: 2021, Volume and Issue: 51(7), P. 1566 - 1579

Published: April 26, 2021

Abstract NK cells are cytotoxic components of innate lymphoid (ILC) that provide a first line defense against viral infections and contribute to control tumor growth metastasis. Their function is finely regulated by an array HLA‐specific non‐HLA‐specific inhibitory activating receptors which allow discriminate between healthy altered cells. Human gained major attention in recent years because the important progresses understanding their biology some promising data therapy. In this review, we will outline well‐established issues human discuss open questions, debates, advances regarding origin, differentiation, tissue distribution. Newly defined cell specializations, including impact checkpoints on function, crosstalk with other types, remarkable adaptive features acquired response certain virus also be discussed.

Language: Английский

Citations

124
Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19 DOI Creative Commons
Hannes Vietzen, Alexander Zoufaly, Marianna Traugott

et al.

Genetics in Medicine, Journal Year: 2021, Volume and Issue: 23(5), P. 963 - 967

Published: Jan. 26, 2021

Language: Английский

Citations

116
A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity DOI Creative Commons
Ren Yang,

Yao Deng,

Baoying Huang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: May 31, 2021

Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective to ensure fair equitable supply all countries. Here, we report on the development highly efficacious mRNA vaccine, SW0123 that composed sequence-modified encoding full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex (LPP) nanoparticles. easy produce using large-scale microfluidics-based apparatus. The unique nanoparticle facilitates vaccine uptake demonstrates high colloidal stability, desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations mice nonhuman primates revealed strong immunogenicity SW0123, represented by induction Th1-polarized T cell responses levels antibodies were capable neutralizing not only wild-type SARS-CoV-2, but also panel variants including D614G N501Y variants. In addition, conferred protection both non-human challenge. Taken together, promising candidate holds prospects further evaluation humans.

Language: Английский

Citations

109