Boosting innate immunity during SARS-CoV-2 clearance

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Abhishesh Kumar Mehata ◽  
Deepa Dehari ◽  
Anuj Kumar Mehta ◽  
Alim Miya

: Currently, humanity is suffering from a highly contagious and infectious novel coronavirus disease. Due to the unavailability of any specifically approved therapy to eradicate this pathogenic virus, day by day, it is claiming more and more life of the humans. By observing the current scenario, human civilization seems to be in dangerous situations, and the development of a potential vaccine against this invisible enemy may take some more time. It was observed that the individual immune system plays an important role in the fighting against the novel coronavirus. Additionally, the innate immune system of the host acts as the first line of defense against invading pathogenic viruses. The host innate immune cells can to detect and detoxify the evading viruses. Thus, boosting the innate immune response via targeting activator or inhibitory immune check points pathways for enhancing T-cell immune response that may potentially help the patients to fight against this deadly virus. The aim of this editorial is to discuss in brief about pathogenesis of COVID-19, role of innate immunity and autophagy during viral clearance.

2019 ◽  
Vol 20 (13) ◽  
pp. 3357
Author(s):  
Yang Xu ◽  
Huan Zhao ◽  
Yang Tian ◽  
Kaixia Ren ◽  
Nan Zheng ◽  
...  

Protein kinase C-δ (PKC-δ) is an important protein in the immune system of higher vertebrates. Lampreys, as the most primitive vertebrates, have a uniquevariable lymphocyte receptor (VLR) immune system. PKC-δ-like is a crucial functional gene in lampreys and is highly expressed in their immune organs. In this study, lampreys were stimulated with different immunogens, and lipopolysaccharide (LPS) was found to increase the expression of PKC-δ-like. Overexpression of PKC-δ-like could also effectively activate the innate immune response. We further demonstrated that PKC-δ-like-CF, a catalytic fragment of PKC-δ-like, is responsible for activating the innate immune response, and Thr-211, which is Thr-419 of PKC-δ-like, was confirmed to be the key site affecting PKC-δ-like-CF activity. These results indicated that PKC-δ-like from lamprey may have an important role in the innate immune response.


Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 313
Author(s):  
Daniel Sepulveda-Crespo ◽  
Salvador Resino ◽  
Isidoro Martinez

Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the global control of the virus in the absence of an effective preventive vaccine. Current vaccine development is mostly focused on weakly immunogenic subunits, such as surface glycoproteins or non-structural proteins, in the case of HCV. Adjuvants are critical components of vaccine formulations that increase immunogenic performance. As we learn more information about how adjuvants work, it is becoming clear that proper stimulation of innate immunity is crucial to achieving a successful immunization. Several hepatic cell types participate in the early innate immune response and the subsequent inflammation and activation of the adaptive response, principally hepatocytes, and antigen-presenting cells (Kupffer cells, and dendritic cells). Innate pattern recognition receptors on these cells, mainly toll-like receptors, are targets for new promising adjuvants. Moreover, complex adjuvants that stimulate different components of the innate immunity are showing encouraging results and are being incorporated in current vaccines. Recent studies on HCV-vaccine adjuvants have shown that the induction of a strong T- and B-cell immune response might be enhanced by choosing the right adjuvant.


2021 ◽  
Vol 10 (3) ◽  
pp. 2402-2413

Currently, a novel coronavirus disease 2019 (COVID 19) caused by SARS-CoV-2 has emerged worldwide. This chronic viral infection causes an acute respiratory distress syndrome (ARDS) which its pathophysiology is not yet well elucidated. However, ARDS has shown that ARDS causes diffuse alveolar damages induced by an excessive inflammatory response and a lack of anti-inflammatory response to the virus. Furthermore, these pathophysiological characteristics are associated with multiorgan failure and can increase the mortality rate. The difference in immune system response against COVID-19 is not well known. However, variability in innate immune system receptors between patients infected with SARS-CoV-2 as a function of aging and sex can explain this difference. Thus, innate immune memory or trained immunity mediated by epigenetic mechanisms is also involved in the variability response against COVID-19. The action of an adaptative immune response, in particular, antigen presentation via HLA is also a key element in this variability. Finally, each viral strain's capacity in evading the action of the immune response has also been suggested as an important mechanism by which certain patients infected with SARS-CoV-2 develop severity and others did not develop any clinical symptoms.


2020 ◽  
Vol 8 (1) ◽  
pp. e000695 ◽  
Author(s):  
Carla V Rothlin ◽  
Sourav Ghosh

The immune system evolved for adequate surveillance and killing of pathogens while minimizing host damage, such as due to chronic or exaggerated inflammation and autoimmunity. This is achieved by negative regulators and checkpoints that limit the magnitude and time course of the immune response. Tumor cells often escape immune surveillance and killing. Therefore, disrupting the brakes built into the immune system should effectively boost the anticancer immune response. The success of anti-CTLA4, anti-PD-1 and anti-PD-L1 have firmly established this proof of concept. Since the response rate of anti-CTLA4, anti-PD-1 and anti-PD-L1 is still limited, there is an intense effort for the identification of new targets and development of approaches that can expand the benefits of immunotherapy to a larger patient pool. Additional T cell checkpoints are obvious targets; however, here we focus on the unusual suspects—cells that function to initiate and guide T cell activity. Innate immunity is both an obligate prerequisite for the initiation of adaptive immune responses and a requirement for the recruitment of activated T cells to the site of action. We discuss some of the molecules present in innate immune cells, including natural killer cells, dendritic cells, macrophages, myeloid-derived suppressor cells, endothelial cells and stromal cells, that can activate or enhance innate immune cell functions, and more importantly, the inhibitors or checkpoints present in these cells that restrain their functions. Boosting innate immunity, either by enhancing activator functions or, preferably, by blocking the inhibitors, may represent a new anticancer treatment modality or at least function as adjuvants to T cell checkpoint inhibitors.


2006 ◽  
Vol 273 (1600) ◽  
pp. 2571-2574 ◽  
Author(s):  
Ben M Sadd ◽  
Michael T Siva-Jothy

It has been a long-held assumption that the innate immune system of insects causes self-harm when used to combat an immune insult. We show empirically that this assumption is correct. Invertebrate innate immunity relies heavily on effector systems which, on activation, produce cytotoxins that kill pathogens. Reliance on these robust, fast-acting, generic killing mechanisms ensures a potent and rapid response to pathogen invasion, but has the potential disadvantage of causing self-damage. We show that the innate immune response against an immune insult produces measurable phenotypic and functional damage to self-tissue in the beetle Tenebrio molitor . This type of self-harm (autoreactivity) and the life-history implications that arise from it are important to understand evolutionary phenomena such as the dynamics between hosts and parasites as well as the nature of immune system costs.


Author(s):  
MURUGAN NANDAGOPAL ◽  
ARULMOZHI BALAKRISHNAN ◽  
CHIRAYU PADHIAR

The coronavirus disease-2019 (COVID-19) outbreak by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or a novel coronavirus (2019-CoV) has prompted global health concerns. A pandemic resulted from the disease’s transmission through many routes. In this pandemic, the interaction between coronavirus and the host immune system, particularly the innate immune system, is becoming more prominent. Against viruses and pathogens, innate immunity serves as a first line of defense. Our understanding of pathogenesis will benefit from a better grasp of the mechanisms of immune evasion techniques. The origin, classification, structure, and method of transmission of SARS-CoV-2 were summarized in this paper. We have discussed the importance of important communications. In this review, we have discussed the function of important components of the innate immune system in COVID-19 infection, as well as how the virus evades innate immunity through multiple tactics and contributes to a wide range of clinical symptoms and outcomes.


Author(s):  
S. G. Gorbunov ◽  
L. N. Mazankova ◽  
A. N. Os’kin

The article reflects the literature data on the immune response mechanisms to rotavirus infection. The authors note that innate immunity factors play the leading role in protecting the organism from rotavirus. They demonstrate that both cellular and humoral components of the immune system are important in the pathogenesis of rotavirus infection. The protective effect is based on the activation of interferon and other cytokines, as well as TLR – innate immune receptor for double-stranded rotavirus RNA. The authors also describe the age-related aspects of the immune response, which cause a higher susceptibility to rotavirus in the neonatal period and its reduction with age.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaomeng Xu ◽  
Yongjun Jiang

Immune system plays an elementary role in the pathophysiological progress of ischemic stroke. It consists of innate and adaptive immune system. Activated within minutes after ischemic onset, innate immunity is responsible for the elimination of necrotic cells and tissue repair, while it is critically involved in the initiation and amplification of poststroke inflammation that amplifies ischemic damage to the brain tissue. Innate immune response requires days to be fully developed, providing a considerable time window for therapeutic intervention, suggesting prospect of novel immunomodulatory therapies against poststroke inflammation-induced brain injury. However, obstacles still exist and a comprehensive understanding of ischemic stroke and innate immune reaction is essential. In this review, we highlighted the current experimental and clinical data depicting the innate immune response following ischemic stroke, mainly focusing on the recognition of damage-associated molecular patterns, activation and recruitment of innate immune cells, and involvement of various cytokines. In addition, clinical trials targeting innate immunity were also documented regardless of the outcome, stressing the requirements for further investigation.


2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Federica Moalli ◽  
Sebastien Jaillon ◽  
Antonio Inforzato ◽  
Marina Sironi ◽  
Barbara Bottazzi ◽  
...  

Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognise pathogen-associated molecular patterns (PAMPs) and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a nonredundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the cross-road between innate immunity, inflammation, and female fertility. Here, we review the studies on PTX3, with emphasis on pathogen recognition and cross-talk with other components of the innate immune system.


Open Biology ◽  
2012 ◽  
Vol 2 (4) ◽  
pp. 120015 ◽  
Author(s):  
Clare E. Bryant ◽  
Tom P. Monie

The innate immune response is the first line of defence against infection. Germ-line-encoded receptors recognize conserved molecular motifs from both exogenous and endogenous sources. Receptor activation results in the initiation of a pro-inflammatory immune response that enables the resolution of infection. Understanding the inner workings of the innate immune system is a fundamental requirement in the search to understand the basis of health and disease. The development of new vaccinations, the treatment of pathogenic infection, the generation of therapies for chronic and auto-inflammatory disorders, and the ongoing battle against cancer, diabetes and atherosclerosis will all benefit from a greater understanding of innate immunity. The rate of knowledge acquisition in this area has been outstanding. It has been underpinned and driven by the use of model organisms. Information obtained from Drospohila melanogaster , knock-out and knock-in mice, and through the use of forward genetics has resulted in discoveries that have opened our eyes to the functionality and complexity of the innate immune system. With the current increase in genomic information, the range of innate immune receptors and pathways of other species available to study is rapidly increasing, and provides a rich resource to continue the development of innate immune research. Here, we address some of the highlights of cross-species study in the innate immune field and consider the benefits of widening the species-field further.


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