SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147 DOI Creative Commons

Shaimaa Shouman,

Nada Elkholy,

Alaa E. Hussien

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 4, 2024

T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While indicates an active anti-viral response, is sign of poor prognosis. T-cells, essence, rarely express ACE2 receptors, making cause cell depletion enigmatic. Moreover, emerging strains posed immunological challenge, potentially alarming for next pandemic. Herein, we review how possible indirect direct key mechanisms could contribute SARS-CoV-2-associated-lymphopenia. The fundamental mechanism inflammatory cytokine storm elicited by viral infection, which alters host metabolism into more acidic state. This "hyperlactic acidemia" together suppresses T-cell proliferation triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results shift from steady-state hematopoiesis stress hematopoiesis. Even low expression, presence cholesterol-rich lipid rafts on activated T-cells may enhance entry syncytia formation. Finally, indicate participation other receptors or auxiliary proteins that can work alone concert mechanisms. Therefore, address CD147-a novel route-for its new variants. CD147 not only expressed but it interacts co-partners orchestrate various biological processes. Given these features, appealing candidate pathogenicity. Understanding molecular cellular behind SARS-CoV-2-associated-lymphopenia will aid discovery potential therapeutic targets improve resilience our immune system against this rapidly evolving virus.

Language: Английский

Sensing of SARS-CoV-2 by pDCs and their subsequent production of IFN-I contribute to macrophage-induced cytokine storm during COVID-19 DOI Creative Commons
Paôline Laurent, Chao Yang, André F. Rendeiro

et al.

Science Immunology, Journal Year: 2022, Volume and Issue: 7(75)

Published: Sept. 9, 2022

Lung-infiltrating macrophages create a marked inflammatory milieu in subset of patients with COVID-19 by producing cytokine storm, which correlates increased lethality. However, these are largely not infected SARS-CoV-2, so the mechanism underlying their activation lung is unclear. Type I interferons (IFN-I) contribute to protecting host against SARS-CoV-2 but may also have some deleterious effect, and source IFN-I lungs well defined. Plasmacytoid dendritic cells (pDCs), key cell type involved antiviral responses, can produce response SARS-CoV-2. We observed infiltration pDCs SARS-CoV-2–infected patients, correlated strong signaling macrophages. In severe COVID-19, expressed robust signature, persistent at single-cell level. Hence, we uncoupling kinetics associated storm that were dominant IFN-α–producing virus blood, whereas produced IFN-α only when physical contact epithelial cells. showed pDCs, after sensing TLR7, mediated changes both transcriptional epigenetic levels, favored hyperactivation environmental stimuli. Together, data indicate priming result from leading macrophage COVID-19.

Language: Английский

Citations

61
The pathogenesis of coronavirus-19 disease DOI Creative Commons
Alain Borczuk, Rhonda K. Yantiss

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Oct. 26, 2022

Abstract Severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) is the causal agent of coronavirus disease-2019 (COVID-19), a systemic illness characterized by variably severe pulmonary symptoms, cardiac conduction abnormalities, diarrhea, and gastrointestinal bleeding, as well neurologic deficits, renal insufficiency, myalgias, endocrine other perturbations that reflect widespread microvascular injury pro-inflammatory state. The mechanisms underlying various manifestations viral infection are incompletely understood but most data suggest COVID-19 results from virus-driven in immune system resultant tissue injury. Aberrant interferon-related responses lead to alterations cytokine elaboration deplete resident cells while simultaneously recruiting hyperactive macrophages functionally altered neutrophils, thereby tipping balance adaptive immunity innate immunity. Disproportionate activation these neutrophils further depletes normal activity B-cells, T-cells, natural killer (NK) cells. In addition, this state stimulates uncontrolled complement development neutrophil extracellular traps (NETS), both which promote coagulation cascade induce “thrombo-inflammation”. These have similar multiple organ systems, frequently show pathologic findings related thrombosis large small vessels. However, patients with generally more pronounced than those organs. Not only do they feature inflammatory thromboses endothelial injury, much parenchymal damage stems failed maturation alveolar pneumocytes, interactions between type 2 pneumocytes non-resident macrophages, greater degree NET formation. purpose review discuss pathogenesis can occur SARS-CoV-2 infection. Understanding important future therapies for COVID-19, many will likely target specific components system, particularly induction, cytokines, subpopulations

Language: Английский

Citations

55
Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments DOI Creative Commons
Zhimei Liu, Minghui Yang, Kun Yu

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 7, 2022

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) rapidly infects humans and animals which make disease 2019 (COVID-19) a grievous epidemic worldwide broke out in 2020. According to data analysis of the other family, for instance severe SARS (SARS-CoV), can provide experience mutation SARS-CoV-2 prevention treatment COVID-19. Toll-like receptors (TLRs) as pattern recognition receptor (PRRs), have an indispensable function identifying invader even activate innate immune system. It is possible organism different TLR pathways leads secretion proinflammatory cytokines such Interleukin 1 (IL-1), 6 (IL-6), Tumor necrosis factor α (TNFα) Ⅰ interferon. As component non-specific immunity, TLRs pathway may participate pathogenic processes, due previous works proved that are involved invasion infection SARS-CoV MERS varying degrees. Different TLR, TLR2, TLR4, TLR7, TLR8 TLR9 probably double-sided COVID-19 infection. Therefore, it great significance correctly acknowledging how take part will be development strategies.

Language: Английский

Citations

48
Inflammatory pathways in COVID‐19: Mechanism and therapeutic interventions DOI
Yujie Jiang, Tingmei Zhao, Xueyan Zhou

et al.

MedComm, Journal Year: 2022, Volume and Issue: 3(3)

Published: Aug. 1, 2022

The 2019 coronavirus disease (COVID-19) pandemic has become a global crisis. In the immunopathogenesis of COVID-19, SARS-CoV-2 infection induces an excessive inflammatory response in patients, causing cytokine storm severe cases. Cytokine leads to acute respiratory distress syndrome, pulmonary and other multiorgan failure, which is important cause COVID-19 progression even death. Among them, activation pathways major factor generating storms dysregulated immune responses, closely related severity viral infection. Therefore, elucidation signaling pathway providing otential therapeutic targets treatment strategies against COVID-19. Here, we discuss pathogenesis including induction, function, downstream signaling, as well existing potential interventions targeting these cytokines or pathways. We believe that comprehensive understanding regulatory dysregulation inflammation will help develop better clinical therapy effectively control diseases, such

Language: Английский

Citations

45
Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses DOI Open Access

Jeffrey Tomalka,

Mehul S. Suthar, Steven G. Deeks

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(3), P. 360 - 370

Published: Feb. 24, 2022

Language: Английский

Citations

40
Tissue factor in COVID-19-associated coagulopathy DOI Creative Commons
Saravanan Subramaniam, Hema Kothari, Markus Bosmann

et al.

Thrombosis Research, Journal Year: 2022, Volume and Issue: 220, P. 35 - 47

Published: Oct. 1, 2022

Language: Английский

Citations

39
Platelets and SARS-CoV-2 During COVID-19: Immunity, Thrombosis, and Beyond DOI Open Access

Anthony R. Sciaudone,

Heather A. Corkrey,

Fiachra Humphries

et al.

Circulation Research, Journal Year: 2023, Volume and Issue: 132(10), P. 1272 - 1289

Published: May 11, 2023

COVID-19 is characterized by dysregulated thrombosis and coagulation that can increase mortality in patients. Platelets are fast responders to pathogen presence, alerting the surrounding immune cells contributing intravascular coagulation. The SARS-CoV-2 genome has been found platelets from patients with COVID-19, its coverage varies according method of detection, suggesting direct interaction virus these cells. Antibodies against Spike Nucleocapsid have confirmed this platelet-viral interaction. This review discusses immune, prothrombotic, procoagulant characteristics observed COVID-19. We outline indirect SARS-CoV-2, contribution programmed cell death pathway activation consequent extracellular vesicle release. discuss platelet immunothrombosis effect on platelets, possible classical triggers as well complement activation. As COVID-19-mediated still not understood vivo, we available murine models mouse adaptable strains.

Language: Английский

Citations

39
TLR8 escapes X chromosome inactivation in human monocytes and CD4+ T cells DOI Creative Commons
Ali Youness, Claire Cénac, Bérénice Faz-Lopez

et al.

Biology of Sex Differences, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 18, 2023

Human endosomal Toll-like receptors TLR7 and TLR8 recognize self non-self RNA ligands, are important mediators of innate immunity autoimmune pathogenesis. are, respectively, encoded by adjacent X-linked genes. We previously established that evades X chromosome inactivation (XCI) in female immune cells. Whether also XCI, however, has not yet been explored.

Language: Английский

Citations

23
Components, Formulations, Deliveries, and Combinations of Tumor Vaccines DOI
Tengfei Liu,

Wenyan Yao,

Wenyu Sun

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(29), P. 18801 - 18833

Published: July 9, 2024

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating restoring the body's own immune system. Currently, various formulations vaccines have been developed, including cell membrane DNA mRNA polypeptide virus-vectored and tumor-in-situ vaccines. There are also multiple delivery systems for such as liposomes, vesicles, viruses, exosomes, emulsions. In addition, to decrease risk escape tolerance that may exist with a single vaccine, combination therapy radiotherapy, chemotherapy, checkpoint inhibitors, cytokines, CAR-T therapy, photoimmunotherapy is effective strategy. Given critical role in here, we look back history discuss antigens, adjuvants, formulations, systems, mechanisms, future directions

Language: Английский

Citations

10
Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19 DOI Creative Commons
Rebeka Fekete, Alba Simats, Eduárd Bíró

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

COVID-19 is associated with diverse neurological abnormalities, but the underlying mechanisms are unclear. We hypothesized that microglia, resident immune cells of brain, centrally involved in this process. To study this, we developed an autopsy platform allowing integration molecular anatomy, protein and mRNA datasets postmortem mirror blocks brain peripheral organ samples from cases COVID-19. observed focal loss microglial P2Y12R, CX3CR1-CX3CL1 axis deficits metabolic failure at sites virus-associated vascular inflammation severely affected medullary autonomic nuclei other areas. Microglial dysfunction linked to mitochondrial injury excessive synapse myelin phagocytosis glutamatergic terminals, line proteomic changes assembly, metabolism neuronal injury. Furthermore, regionally heterogeneous viral load central systemic related interleukin (IL)-1 or IL-6 via virus-sensing pattern recognition receptors inflammasomes. Thus, SARS-CoV-2-induced might lead a primarily gliovascular which could be common contributor COVID-19-related neuropathologies.

Language: Английский

Citations

1