Bronchoalveolar lavage single-cell transcriptomics reveals immune dysregulations driving COVID-19 severity

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0309880 - e0309880

Published: Feb. 10, 2025

The continuous threats posed by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, including emergence of potentially more infectious and deadly variants, necessitate ongoing studies to uncover novel detailed mechanisms driving disease severity. Using single-cell transcriptomics, we conducted a secondary data analysis bronchoalveolar lavage fluid (BALF) from COVID-19 patients varying severities healthy controls comprehensively examine immune responses. We observed significant cell alterations correlating with In severe cases, macrophages showed upregulation pro-inflammatory genes TNFα IL1β, contributing inflammation tissue damage. Neutrophils exhibited increased activation, marked S100A8, CXCL8, IL1β expression, extended viability reduced phagocytosis. Genes such as MCL1 HIF1α supported viability, while MSR1 MRC1 indicated Enhanced formation neutrophil extracellular traps (NETs) clearance, NET-associated markers, were linked thrombo-inflammation organ Both neutrophils in cases impaired efferocytosis, decreased expression TREM2 downregulation FCGR3B neutrophils, leading accumulation apoptotic cells exacerbating inflammation. characterized M1 high milder had M2 elevated PPARγ. Dendritic (DCs) proportions attenuated MHC class I (HLA-A, HLA-B, HLA-C) co-stimulatory molecules (CD80, CD86), alongside cytochrome c indicating antigen presentation enhanced apoptosis. NK T demonstrated altered receptor gene activation markers IFNγ ISG15, suggesting paradoxical state exhaustion. This highlights critical role dysregulated neutrophil, macrophage, dendritic cell, NK, responses identifying potential therapeutic targets providing insights into disease.

Language: Английский

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Exploring Interleukin-6 Inhibitor Antibodies in Combatting SARS-CoV-2 and Its Mutated Variants: Challenges and Future Directions

Journal of Pharmacology and Pharmacotherapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

The aim of this study is to investigate the efficacy interleukin-6 (IL-6) inhibitor antibodies as a therapeutic agent combat severe COVID-19. Given constant evolution acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, aims assess potential these inhibitors in adapting new challenges improving treatment outcomes. A comprehensive review relevant literature was conducted using electronic databases such Web Science, PubMed, EMBASE, Scopus, Google Scholar. analyzed role IL-6 combating SARS-CoV-2, focusing on their treating COVID-19 cases, particularly controlling overshooting immune response associated with cytokine storms. proved be versatile effective attenuating responses, especially storms, which are common advanced cases. emphasizes ability regulate system, reduce disease severity, improve patient Their reducing severity makes promising strategy for SARS-CoV-2 variants. Further research needed optimize use adaptability evolving clinical scenarios.

Language: Английский

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Pulmonary Myeloid Cells in Mild Cases of COVID-19 Upregulate the Intracellular Fc Receptor TRIM21 and Transcribe Proteasome-Associated Molecules

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2769 - 2769

Published: March 19, 2025

Much remains to be understood about COVID-19, but the protective role of antibodies (Igs) is widely accepted in SARS-CoV-2 infection. Igs’ functions are mainly carried out by receptors that bind their Fc portion (FcR), and less attention has been dedicated cytoplasmic members this family. In work, we used single-cell RNA sequencing (scRNA-seq) data discern cell populations bronchoalveolar lavage fluid obtained from healthy individuals patients with mild or severe COVID-19. Then, evaluated transcription neonatal FcR (FcRn, FCGRT gene) tripartite motif-containing protein 21 (TRIM21) its downstream signaling components. The TRIM21 pathway vital for virus infections as it a dual function, leading opsonized viruses degradation proteasomes activation innate inflammatory anti-virus response. transcriptional level showed no statistical differences any population comparing three groups patients. On other hand, was significantly higher myeloid cells collected When cases, there difference lung adaptive lymphoid (ILC). Yet, analyzed all molecules and, most expressed receptor, cells. Moreover, ILCs cases were missing components pathway. We observed ubiquitin–proteasome system (UPS) associated proteasomal transcribed cases. Despite danger sensors DDX58 IFIH1, IL1B IL18 generally very low, along NLRP3 sensor, NF-κB pathway, TNF. Therefore, our suggest may contribute protection reducing viral load, while branch would silenced, pathogenic cytokine production.

Language: Английский

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IMMUNE SYSTEM DISTANT EFFECTS IN PATIENTS WITH LONG-COVID ON THE BACKGROUND OF REACTIVATION HHV-6 INFECTION

Immunology and Allergy Science and Practice, Journal Year: 2025, Volume and Issue: 1, P. 31 - 42

Published: April 7, 2025

Introduction. It is now known that 30% of patients who have recovered from COVID-19 develop long-COVID. According to researchers, the reactivation herpesviruses plays a significant role in triggering In these patients, alteration lymphocyte populations and T-lymphocyte subpopulations been observed, yet nature changes remains unclear. The dysregulation immune response caused by SARS-CoV-2 further exacerbated human herpesvirus type 6 (HHV-6). Therefore, it essential distinguish alterations long-COVID based on HHV-6 consider differences when developing therapeutic approaches. aims this study were: 1) investigate associative relationships between number populations, subpopulations, severity clinical course with long-COVID; 2) determine compare percentages CD3+, CD4+, CD56+, CD8+, CD4/25/127– T-regs CD19+ cells depending presence reactivated HHV-6. Materials methods. our study, we examined 124 including 73 women (59%) 51 men (41%), an average age 43±9.70 years, all whom had suffered second half 2023. To confirm form groups, molecular genetic studies (PCR) were conducted patients. Subsequently, flow cytometry was used analyze peripheral blood samples Results. following severe COVID-19, percentage CD3+ T cells, CD8+ CD4+CD25+CD127– significantly lower both absence (p=0.014; p=0.016; p=0.045, respectively) during active phase (p=0.045; p=0.005; p=0.008, respectively), compared control group. CD4+ decreased only (p=0.045). Notably, HHV-6, reduced those without reactivation. Additionally, B elevated reactivation, group (p<0.0001) (p=0.0002). Furthermore, CD56+ NK long- COVID mild moderate history, did not differ However, after context (p=0.0001). Conclusions. Our data development This mediated through adaptive cell interactions, activation NF-κB signaling pathway, increased production antibodies defective structure. Based results, may risk immunopathological complications, potentially autoimmune disorders. These findings offer valuable insights for future research potential strategies.

Language: Английский

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SM3DD with Segmented PCA: A Comprehensive Method for Interpreting 3D Spatial Transcriptomics

Published: April 18, 2025

Abstract We developed Standardised Minimum 3D Distance (SM3DD), an entirely cell segmentation/annotation-free approach to the analysis of spatial RNA datasets, using it compare lung tissue from 16 clinically normal individuals those 18 SARS-CoV-2 patients who died acute respiratory distress syndrome. coordinates were determined CosMx™ Spatial Molecular Imager (Bruker Biology, US). For each individual transcript location, we calculated three-dimensional distances nearest type, standardising type. Mean SM3DDs compared between and patients. Notably, hierarchical clustering directional log10(P) values organized genes by functionality, making easier interpret biological contexts for FKBP11, where a decrease in distance MZT2A was most significant difference, suggesting role interferon signaling. Using segmented principal components entire SM3DD dataset, identified multiple pathways, including ‘SARS-CoV-2 infection’, even though assay did not include any transcripts.

Language: Английский

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Chitosan as Tools to Combat COVID-19

Published: Jan. 1, 2025

Language: Английский

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Low-dose IL-2 therapy in autoimmune diseases: An update review

International Reviews of Immunology, Journal Year: 2023, Volume and Issue: 43(3), P. 113 - 137

Published: Oct. 26, 2023

Regulatory T (Treg) cells are essential for maintaining self-immune tolerance. Reduced numbers or functions of Treg have been involved in the pathogenesis various autoimmune diseases and allograft rejection. Therefore, approaches that increase pool suppressive function

Language: Английский

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Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 13, 2024

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in disease, often characterised by a ‘cytokine storm’ and the associated distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout course of infection. Although blood biomarkers disease well studied, less understood inflammatory signatures lung tissues silent infections, wherein infection inflammation rapidly resolved leading to sequelae-free recovery. Herein we described RNA-Seq histological analyses lungs over time an omicron BA.1/K18-hACE2 mouse model, displays these latter features. robust was evident at days post (dpi), viral RNA largely cleared 10 dpi. Acute showed slightly different pattern cytokine compared models, where much diminished 30 dpi absent 66 Cellular deconvolution identified significantly increased abundance scores for number anti-inflammatory pro-resolution cell types 5/10 These included type II innate lymphoid cells, T regulatory interstitial macrophages. Genes whose expression trended downwards – were pathways. upward during this period recovery ciliated AT2 AT1 transition, reticular fibroblasts indicating return homeostasis. Very few differentially expressed host genes dpi, suggesting near complete parallels between subclinical humans those observed model discussed reference concept “protective inflammation”.

Language: Английский

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Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: June 24, 2024

Autism spectrum disorder (ASD 1 ) is a behaviorally defined syndrome encompassing markedly heterogeneous patient population. Many ASD subjects fail to respond the st line behavioral and pharmacological interventions, leaving parents seek out other treatment options. Evidence supports that neuroinflammation plays role in pathogenesis. However, underlying mechanisms likely vary for each patient, influenced by genetic, epigenetic, environmental factors. Although anti-inflammatory measures, mainly based on metabolic changes oxidative stress, have provided promising results some subjects, use of such measures requires careful selection clinical laboratory findings. Recent progress neuroscience molecular immunology has made it possible allow re-purposing currently available medications, used autoimmune chronic inflammatory conditions, as options subjects. On hand, emerging including biologic gate-keeper blockers, exert powerful effects specific mediators or signaling pathways. It will require both keen understanding action agents patients suitable treatment. This review attempt summarize already targeting patients, then applicable scientific rationale trial data, if available. In our experience, were treated under diagnoses autoimmune/autoinflammatory conditions and/or post-infectious neuroinflammation. there are little data specifically Therefore, these immunomodulating potential be discussed preclinical case reports, generated with medical conditions. hopefully highlight expanding scope treating

Language: Английский

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The Major Role of T Regulatory Cells in the Efficiency of Vaccination in General and Immunocompromised Populations: A Review

Vaccines, Journal Year: 2024, Volume and Issue: 12(9), P. 992 - 992

Published: Aug. 30, 2024

Since their conception with the smallpox vaccine, vaccines used worldwide have mitigated multiple pandemics, including recent COVID-19 outbreak. Insightful studies uncovered complexities of different functional networks CD4 T cells (T helper 1 (Th1); Th2, Th17) and CD8 cytotoxic; Tc), as well B cell (B

Language: Английский

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