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

Innate immune evasion strategies of SARS-CoV-2 DOI Open Access
Judith M. Minkoff, Benjamin R. tenOever

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 11, 2023

Language: Английский

Citations

165

Immune response in COVID-19: what is next? DOI Creative Commons
Qing Li, Ying Wang, Qiang Sun

et al.

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(6), P. 1107 - 1122

Published: May 17, 2022

Abstract The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle quality in unprecedented ways. A better understanding of immunity its regulation response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here various virus mutations evolving manifestations along with alterations immune responses specific focuses innate response, neutrophil extracellular traps, humoral immunity, cellular immunity. Different types vaccines were compared analyzed based their unique properties elicit Various therapeutic strategies such as antibody, anti-viral medications inflammation control discussed. We predict that available continuously emerging new technologies, powerful administration schedules, effective public health measures, COVID-19 will be under near future.

Language: Английский

Citations

114

Type I interferons and SARS-CoV-2: from cells to organisms DOI Creative Commons
Paul Bastard, Qian Zhang, Shen‐Ying Zhang

et al.

Current Opinion in Immunology, Journal Year: 2022, Volume and Issue: 74, P. 172 - 182

Published: Jan. 25, 2022

Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type IFNs SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of IFNs, proteins can inhibit various steps IFN production response. Exogenous viral growth vitro. In animal species vivo, deficiencies underlie higher loads more severe disease than control animals. The early administration exogenous improves infection control. humans, inborn errors of, auto-antibodies against life-threatening COVID-19 pneumonia. Overall, are essential for host defense individual whole organisms.

Language: Английский

Citations

71

Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases DOI Creative Commons

Sareh Kakavandi,

Iman Zare, Maryam Vaezjalali

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 15, 2023

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in genome this virus. S, M, H, E proteins, NSPs include accessory replicase proteins. The NSP components SARS-CoV-2 play an important role its infectivity, some them may be pathogenesis chronic diseases, including cancer, coagulation disorders, neurodegenerative cardiovascular diseases. interact with targets such angiotensin-converting enzyme (ACE2) receptor. In addition, can stimulate pathological intracellular signaling pathways triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, Eph receptors, which roles progression diseases like Alzheimer's disease, epilepsy, multiple sclerosis, cancers glioblastoma, lung malignancies, leukemias. Several compounds polyphenols, doxazosin, baricitinib, ruxolitinib could inhibit these interactions. It has been demonstrated that spike protein stronger affinity for human ACE2 than SARS-CoV, leading current study to hypothesize newly produced variant Omicron receptor-binding domain (RBD) binds more strongly primary strain. SARS Middle East (MERS) viruses against have become resistant previous vaccines. Therefore, review recent studies performance vaccines their effects on COVID-19 related vital need deal conditions. This examines potential initiation it anticipated serve effective vaccine or treatment Video Abstract.

Language: Английский

Citations

67

Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder DOI Open Access
Tsung‐Hsien Chen, Chia-Jung Chang, Peir‐Haur Hung

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8034 - 8034

Published: April 28, 2023

Patients who have recovered from coronavirus disease 2019 (COVID-19) infection may experience chronic fatigue when exercising, despite no obvious heart or lung abnormalities. The present lack of effective treatments makes managing long COVID a major challenge. One the underlying mechanisms be mitochondrial dysfunction. Severe acute respiratory syndrome 2 (SARS-CoV-2) infections can alter mitochondria responsible for energy production in cells. This alteration leads to dysfunction which, turn, increases oxidative stress. Ultimately, this results loss integrity and cell death. Moreover, viral proteins bind complexes, disrupting function causing immune cells over-react. over-reaction inflammation potentially symptoms. It is important note that roles damage inflammatory responses caused by SARS-CoV-2 development are still being elucidated. Targeting provide promising new clinical approaches long-COVID patients; however, further studies needed evaluate safety efficacy such approaches.

Language: Английский

Citations

47

Bat genomes illuminate adaptations to viral tolerance and disease resistance DOI Creative Commons
Ariadna E. Morales, Yue Dong, Tom Brown

et al.

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

Published: Jan. 29, 2025

Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested harbour more zoonotic viruses than any other mammalian order1. Infections in bats largely asymptomatic2,3, indicating limited tissue-damaging inflammation and immunopathology. To investigate the genomic basis of disease resistance, Bat1K project generated reference-quality genomes ten bat species, including potential viral reservoirs. Here we describe a systematic analysis covering 115 that revealed signatures selection immune genes prevalent orders. We found an excess gene adaptations ancestral chiropteran branch many descending lineages, highlighting entry detection factors, regulators antiviral inflammatory responses. ISG15, which is contributing hyperinflammation during COVID-19 (refs. 4,5), exhibits key residue changes rhinolophid hipposiderid bats. Cellular infection experiments show species-specific differences essential role protein conjugation function separate its secretion Furthermore, contrast humans, ISG15 most has strong anti-SARS-CoV-2 activity. Our work reveals molecular mechanisms contribute tolerance resistance A genomes, 10 new positive shows aid bats, coronaviruses.

Language: Английский

Citations

7

Mucosal immune response in biology, disease prevention and treatment DOI Creative Commons
Xiaoxue Zhou, Yuchen Wu,

Zhipeng Zhu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 7, 2025

Abstract The mucosal immune system, as the most extensive peripheral network, serves frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion establishing tolerance. A comprehensive understanding immunity essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing overall impact on body. Despite its importance, our knowledge remains incomplete, necessitating further research. outbreak severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored critical role disease prevention treatment. This systematic review focuses dynamic interactions between mucosa-associated lymphoid structures related diseases. We delve into basic functions these tissues during processes explore intricate regulatory networks mechanisms involved. Additionally, we summarize novel therapies clinical research advances immunity-related also addresses challenges vaccines, which aim to induce specific responses while maintaining tolerance non-pathogenic microbes. Innovative therapies, such nanoparticle vaccines inhalable antibodies, show promise enhancing offer potential improved

Language: Английский

Citations

4

Innate immune sensors and regulators at the blood brain barrier: focus on toll-like receptors and inflammasomes as mediators of neuro-immune crosstalk and inflammation DOI Creative Commons
Çiğdem Acıoğlu, Stella Elkabes

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 15, 2025

Cerebral endothelial cells (CEC) that form the brain capillaries are principal constituents of blood barrier (BBB), main active interface between and which plays a protective role by restricting infiltration pathogens, harmful substances immune into while allowing entry essential nutrients. Aberrant CEC function often leads to increased permeability BBB altering bidirectional communication bloodstream facilitating extravasation brain. In addition their as gatekeepers BBB, exhibit cell properties they can receive transmit signals partly via release inflammatory effectors in pathological conditions. express innate receptors, including toll like receptors (TLRs) inflammasomes first sensors exogenous or endogenous dangers initiators responses drive neural dysfunction degeneration. Accumulating evidence indicates activation TLRs compromises integrity, promotes aberrant neuroimmune interactions modulates both systemic neuroinflammation, common features neurodegenerative psychiatric diseases central nervous system (CNS) infections injuries. The goal present review is provide an overview pivotal roles played discuss molecular cellular mechanisms contribute disruption neuroinflammation especially context traumatic ischemic injuries infections. We will focus on most recent advances literature reports field highlight knowledge gaps. future research directions advance our understanding contribution potential at promising therapeutic targets wide variety conditions

Language: Английский

Citations

3

Exploiting viral sensing mediated by Toll-like receptors to design innovative vaccines DOI Creative Commons
Rossella Sartorius, Maria Trovato, Roberta Manco

et al.

npj Vaccines, Journal Year: 2021, Volume and Issue: 6(1)

Published: Oct. 28, 2021

Abstract Toll-like receptors (TLRs) are transmembrane proteins belonging to the family of pattern-recognition receptors. They function as sensors invading pathogens through recognition pathogen-associated molecular patterns. After their engagement by microbial ligands, TLRs trigger downstream signaling pathways that culminate into transcriptional upregulation genes involved in immune defense. Here we provide an updated overview on members TLR and focus role antiviral response. Understanding innate sensing viruses triggered these would useful knowledge prompt development vaccines able elicit effective long-lasting responses. We describe mechanisms developed viral escape from surveillance mediated finally discuss how TLR/virus interplay might be exploited guide design innovative vaccine platforms.

Language: Английский

Citations

94

Toll-Like Receptors as a Therapeutic Target in the Era of Immunotherapies DOI Creative Commons
Mariya Farooq, Maria Batool, Moon Suk Kim

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Oct. 4, 2021

Toll-like receptors (TLRs) are the pattern recognition receptors, which activated by foreign and host molecules in order to initiate immune response. They play a crucial role regulation of innate immunity, several studies have shown their importance bacterial, viral, fungal infections, autoimmune diseases, cancers. The consensus view from an immunological perspective is that TLR agonists can serve either as possible therapeutic agent or vaccine adjuvant toward cancers infectious diseases inhibitors may be promising approach treatment some cancers, viral infections. These notions based on fact stimulate secretion proinflammatory cytokines general, development responses. Some TLR-based inhibitory agents efficacious preclinical models now entered clinical trials. Therefore, TLRs seem hold potential perfect target era immunotherapies. We offer therapeutics sheds light usefulness combination therapies. also highlight various discovery phase

Language: Английский

Citations

72