Cellular immune states in SARS-CoV-2-induced disease

Mortezaee, Keywan; Majidpoor, Jamal

doi:10.3389/fimmu.2022.1016304

Cited by 8 publications

(4 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They produce anti-inflammatory cytokines, such as Interleukin 10 (IL-10) and Transforming Growth Factor (TGF)-β, and help to limit tissue damage caused by the immune response. In COVID-19, M1 and M2 macrophage-mediated immune responses are unbalanced and often polarised, and this leads to an uncontrolled development of inflammation (Mortezaee K. et al, 2022). The activation of dendritic cells and M1 and M2 macrophages is mediated by a variety of surface markers, including CD markers.…”

Section: Cellular Mechanism Of Ifn Action In Diseasementioning

confidence: 99%

Infection-Simulator, Immunostimulatory and Immunomodulatory Effects of Interferons I and III in Biological Systems: A New Era in Vaccinology and Therapeutics Possible?

Carp,

Metoudi,

Ojha

2024

Preprint

View full text Add to dashboard Cite

The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 and 2022, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses other prevalent alpha/ beta coronaviruses, but also the Middle East Respiratory Syndrome (MERS-CoV) and SARS-CoV-1, with recent SARS–CoV–2 variants, increasing demands for effective immunogens and therapeutic approaches that will reduce global disease burden and further infection from SARS–CoV-2 affected individuals that may experience post acute sequelae (PASC) or “Long COVID”. Following a worldwide programme of prophylactic vaccination, there is still a dilemma in the efforts to find prophylactic and early therapeutic approaches that would treat novel SARS-CoV-2 variants and prevent future epidemics or pandemics within host human and animal populations, where zoonotic or cross species transfer naturally occurs. Concerns about viral immune escape intersect at a specific point; a gained evolutionary ability of several viruses to co–infect and compete against previous scientific advances since 1796 that remain undetected or asymptomatic during the early stages of infection progressing to symptomatic and severe disease through capping of the 5' end of DNA and RNA genomes respectively, which is performed by the activated viral 2’ - O - Methyltransferase (MTase) enzyme, which is a complex of two viral non-structural proteins (NSPs) joined together through an activation process (NSP10/16). Moreover, it was discovered that certain polymorphic viruses translate NSP1, which prevents the activation of various Pattern Recognition Receptors (PRRs), directly silences important interferon-stimulated genes (ISGs), is signalled in a paracrine manner to neighbouring cells, and that induces the apoptosis of host cells, inducing an effect of “trace erase” effect and making the viral infection as immunologically “invisible” as possible during the initial, key stages of viral replication and distribution, all such mechanisms occurring independently of the viruses in cause. Other viral NSPs share a role with NSP1 in directly suppressing the activation of PRRs and ISGs, and all such viral proteins help the virus in its process of self-camouflaging against first- and second-line immunity, thereby often severely impacting the quality of the produced adaptive immune responses. The outcome of all such phenomena is the sharp decrease in the host Type I and Type III interferons' (IFNs) rate of synthesis by the host cells, that would usually occur and affect homeostatic cellular pathways, resulting in further viral replication and induced apoptosis. Nonetheless, effects of microbial immune evasion during the development of other viral or carcinogenic pathologies are not widely known. In short, polymorphic viruses developed a proportionate evolutionary response against developed adaptive immune responses, by currently relying on gaps mostly situated in the natural immune system in their process of molecular self-camouflaging. Scientists developed numerous approaches of early treatment that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration whilst filtering for the most appropriate solutions. For example, the administration of recombinant human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can simulate intracellular infection and stimulate cellular activity in a timely manner, training the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Another example could involve the treatment of natural and adaptive lymphocytes with a low dose of IFNs I and possibly III, prior to their insertion into the host lymphatic system, possibly alongside additional recruitment of plasmacytoid dendritic cells (pDCs) as further interferon “factories”, all with the purpose of early infection management. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. It is until the scientific community realises this potentially crucial aspect that large proportions of the world population will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently, monkeypox and possibly avian flu. Of note, it has been indicated that IFN I and / or III display significant immunising, early therapeutic and clinical disease onset-attenuating effects for many other microbial evoked diseases, as well as for a number of oncological diseases.

show abstract

Section: Cellular Mechanism Of Ifn Action In Diseasementioning

confidence: 99%

Infection-Simulator, Immunostimulatory and Immunomodulatory Effects of Interferons I and III in Biological Systems: A New Era in Vaccinology and Therapeutics Possible?

Carp,

Metoudi,

Ojha

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…They produce anti-inflammatory cytokines, such as IL-10 and transforming growth factor (TGF)-β, and help to limit tissue damage caused by the immune response. In COVID-19, the M1 and M2 macrophage-mediated immune responses are unbalanced and often polarized, often leading to an uncontrolled development of inflammation (Mortezaee K. et al, 2022). The activation of dendritic cells and M1 and M2 macrophages is mediated by a variety of surface markers, including CD markers.…”

Section: Cellular Mechanism Of Ifn Action In Diseasementioning

confidence: 99%

Low-Dose Interferon I and III-Based Nasal Sprays: A Good-Looking COVID-19 Vaccine Candidate and a Therapy of the Future?

Carp¹,

Metoudi²,

Brown³

et al. 2023

Preprint

View full text Add to dashboard Cite

The SARS–CoV-2 infection has caused both acute and chronic COVID–19 disease during the recent pandemic with emerging more transmissible SARS–CoV–2 Omicron variants (BQ1 and XBB1) that have increased demands for more effective immunogens and therapeutic approaches to protect the lives of numerous SARS–CoV-2 affected individuals and reduce overall disease burden that could be affected by concurrent other pathogens causing diseases. Following a worldwide campaign of mass vaccination, there is still a significant demand to quell the harmful effects of novel SARS–CoV–2 infections due to higher mutation rates within specific areas of the SARS–CoV-2 domain, leading to enhanced viral entry, especially within individuals with one or more significant comorbidities, and there is still a dilemma of how prevention of future pandemics will occur as within host animal mutations and cross species transfer naturally occurs. Concerns intersect at a specific point; a gained evolutionary ability of several viruses over the previous centuries to remain undetected during the first stages of infection by means of capping the 5' end of their DNA and RNA genes respectively. This may occur by reducing the rate of host Type I and Type III Interferons (IFN) cellular synthesis, that would usually occur and affect both apoptotic pathways, that facilitate viral replication and clearance, as well as immune cells, that process and present pathogenic antigen epitopes. Furthermore, although methods of vaccination exist, other methods in clinical development remain that could evoke an immune response in different cellular, serum or mucosal compartments being cellular, serum and mucosal that evoke differential antibody responses. Antibodies are classed as natural and synthetic. Natural antibodies are further classified into neutralizing and non-neutralizing, whilst synthetic antibodies are also further classified into monoclonal and polyclonal. As a result of single cell study transcriptome research, viruses do utilize an array of protein receptors for receptor-mediated cellular entry. This, therefore suggests that potential differential production of antibody immunoglobulins (Ig) within serum and mucosal areas remains affected by cytokines, adhesion molecules and chemokines that can be upregulated or downregulated upon host viral infection. Serum plasma antibodies can be multimeric that may not efficiently cross the nasal epithelium cell layer, therefore offering less protection against mucosal inflammation due to mucin proteins. On the other hand, antibodies produced by mucosal plasma cells at epithelial surfaces are known to provide effective immune responses in some viral infections. The existence of developments that stimulate mucosal immune responses has so far only been seen with influenza nasal immunogens. Nevertheless, scientists developed ways of immunization and early treatment worldwide that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration. For example, the administration of human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can stimulate cellular activity to train the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Recently, it was discovered that specific plants secrete proteins that also stimulate the production of Type I Interferons. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. Naturally-selected polymorphic viruses through genetic recombination pose challenges to traditional concepts of cellular and molecular immune system neutralization of these viruses during the first stages of cellular infection. It is until the scientific community realizes this potentially crucial aspect that we will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently monkeypox. Type I IFNs tend to be produced faster than Type III IFNs, and the first induce slightly more abundant pro-inflammatory signals than the latter, meaning that type III IFNs, if produced early, may further decrease the extent of excessive proinflammatory signals. Hence, we believe that nasal sprays containing a low dosage of Type I and Type III IFNs not only represent a relevant COVID-19 therapeutic, but also a potential unknown modulatory therapy of the future. Of note, it has been indicated that IFN I and / or III display significant immunizing and early therapeutic effects for other viral evoked diseases like Influenza (Influenza (A)H1N1), rabies (Rabies lyssavirus), measles (Measles virus), rubella (Rubivirus rubellae), Hepatitis B, HIV-induced AIDS, Ebola, Marburg, as well as bacterial diseases, such as lower respiratory tract infectious diseases induced by Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus, and a number of oncological diseases, like hepatic melanoma.

show abstract

“…The extent of viral infections and the efficacy of the innate immune response, particularly type I IFNmediated, are critical in determining subsequent adaptive immune response and the clinical outcome. Patients with asymptomatic/mild COVID-19 disease showed a balance production of inflammatory response and virus-specific T-cell activation (40). However, patients with severe COVID-19 were characterized by hyperinflammatory responses with robust production of inflammatory cytokines (39).…”

Section: Adaptive Immunitymentioning

confidence: 99%

Emerging SARS-CoV-2 Variants and Their Impact on Immune Evasion and Vaccine-Induced Immunity

Gupta,

Rao

2023

Preprint

View full text Add to dashboard Cite

The newly emerged variants of SARS-CoV-2 created a potential threat among societies and highlighted one of the significant concerns in facing the pandemic. SARS-CoV-2 variants harboring mutations in the structural protein, especially in the RBD domain of spike protein, have raised concern about potential immune escape. The spike protein of SARS-CoV-2 play a vital role in infection and is an important target for neutralizing antibodies. The mutations that occur in the structural proteins, especially in the spike protein, lead to changes in the virus attributes of transmissibility, an increase in disease severity, a notable reduction in neutralizing antibodies generated, and thus a decreased response to vaccines and therapy. The immune response against SARS-CoV-2 has been reported mainly through innate immune responses rather than adaptive immune responses. SARS-CoV-2 invades the host's innate immunity, possibly through inducing cytokine storm, impairing type I IFN responses, and suppressing antigens presentation to T cells. Therefore, the adaptive immune response is required to combat SARS-CoV-2 infection. The SARS-CoV-2 infections activated both arms of adaptive immunity; humoral and cell-mediated immunity. The observed multiple mutations in the RBD domain of the spike protein compromised the adaptive immune response and showed immune escape because it increases the affinity of spike protein binding with the ACE-2 receptor of host cells and increases resistance to neutralizing antibodies. Cytotoxic T-cell responses are crucial in controlling SARS-CoV-2 infections from the infected tissues and clearing them from circulation. CD8+cytotoxic T cells identify and directly kill the infected cells by releasing soluble mediators perforin and granzymes. The functional exhaustion of cytotoxic T cells may increase the severity of the disease. The expression of activation markers of T cells could indicate hyperactivation or functional exhaustion; the exact implication is not yet understood in SARS-CoV-2 infections. These mutations at critical residues influence the antigenic profile of SARS-CoV-2, which may evade the immune responses and thus reduce the immunogenicity and efficacy of vaccines. Therefore, the spike protein may be recognized as a primary target for vaccines and drugs. This review article summarizes the impact of mutations in the spike protein of SARS-CoV-2, especially mutations of RBD, on immunogenicity, immune escape, and vaccine-induced immunity, which could potentially contribute to future studies focusing on vaccine design and immunotherapy.

show abstract

Cellular immune states in SARS-CoV-2-induced disease

Cited by 8 publications

References 119 publications

Infection-Simulator, Immunostimulatory and Immunomodulatory Effects of Interferons I and III in Biological Systems: A New Era in Vaccinology and Therapeutics Possible?

Infection-Simulator, Immunostimulatory and Immunomodulatory Effects of Interferons I and III in Biological Systems: A New Era in Vaccinology and Therapeutics Possible?

Low-Dose Interferon I and III-Based Nasal Sprays: A Good-Looking COVID-19 Vaccine Candidate and a Therapy of the Future?

Emerging SARS-CoV-2 Variants and Their Impact on Immune Evasion and Vaccine-Induced Immunity

Contact Info

Product

Resources

About