scholarly journals A new perspective for mitigation of SARS-CoV-2 infection: priming the innate immune system for viral attack

Open Biology ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 200138
Author(s):  
Oren Kolodny ◽  
Michael Berger ◽  
Marcus W. Feldman ◽  
Yoav Ram
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune System ◽  
Population Level ◽  
Innate Immune ◽  
Infectious Period ◽  
Individual Level ◽  
New Perspective ◽  
The Individual ◽  
The Impact

The course of infection by SARS-CoV-2 frequently includes a long asymptomatic period, followed in some individuals by an immune dysregulation period that may lead to complications and immunopathology-induced death. This course of disease suggests that the virus often evades detection by the innate immune system. We suggest a novel therapeutic approach to mitigate the infection's severity, probability of complications and duration. We propose that priming an individual's innate immune system for viral attack shortly before it is expected to occur may allow pre-activation of the preferable trajectory of immune response, leading to early detection of the virus. Priming can be carried out, for example, by administering a standard vaccine or another reagent that elicits a broad anti-viral innate immune response. By the time that the expected SARS-CoV-2 infection occurs, activation cascades will have been put in motion and levels of immune factors needed to combat the infection will have been elevated. The infection would thus be cleared faster and with less complication than otherwise, alleviating adverse clinical outcomes at the individual level. Moreover, priming may also mitigate population-level risk by reducing need for hospitalizations and decreasing the infectious period of individuals, thus slowing the spread and reducing the impact of the epidemic. In view of the latter consideration, our proposal may have a significant epidemiological impact even if applied primarily to low-risk individuals, such as young adults, who often show mild symptoms or none, by shortening the period during which they unknowingly infect others. The proposed view is, at this time, an unproven hypothesis. Although supported by robust bio-medical reasoning and multiple lines of evidence, carefully designed clinical trials are necessary.

scholarly journals Insights into Sensing of Murine Retroviruses

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 836
Author(s):  
Eileen A. Moran ◽  
Susan R. Ross
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nucleic Acid ◽  
Adaptive Immunity ◽  
Innate Immune System ◽  
Innate Immune ◽  
Genetic Tool ◽  
Causes Of Disease ◽  
Retrovirus Infection ◽  
Insight Into

Retroviruses are major causes of disease in animals and human. Better understanding of the initial host immune response to these viruses could provide insight into how to limit infection. Mouse retroviruses that are endemic in their hosts provide an important genetic tool to dissect the different arms of the innate immune system that recognize retroviruses as foreign. Here, we review what is known about the major branches of the innate immune system that respond to mouse retrovirus infection, Toll-like receptors and nucleic acid sensors, and discuss the importance of these responses in activating adaptive immunity and controlling infection.

scholarly journals Phenoloxidase activity and haemolymph cytology in honeybees challenged with a virus suspension (deformed wings virus DWV) or phosphate buffered suspension (PBS)

2019 ◽  
Vol 49 (2) ◽  
Author(s):  
Francesca Millanta ◽  
Simona Sagona ◽  
Maurizio Mazzei ◽  
Mario Forzan ◽  
Alessandro Poli ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Innate Immune System ◽  
Innate Immune ◽  
Additional Stress ◽  
Varroa Mite ◽  
Virus Suspension ◽  
Phenoloxidase Activity ◽  
Cell Immunity

ABSTRACT: The innate immune system of honeybees mainly consists in antimicrobial peptides, cellular immunity and melanisation. In order to investigate the immune response of honeybees to immune stressors, three stress degrees were tested. Newly emerged bees naturally DWV-infected were collected from a Varroa mite-free apiary and divided into three experimental groups: naturally DWV infected bees, PBS injected bees, and artificially DWV super infected bees. Phenoloxidase activity and haemolymph cellular subtype count were investigated. Phenoloxidase activity was highest (P<0.05) in DWV-superinfected bees, and the haemocyte population differed within the three observed groups. Although, immune responses following DWV infection have still not been completely clarified, this investigation sheds light on the relation between cell immunity and the phenoloxidase activity of DWV-naturally infected honeybees exposed to additional stress such as injury and viral superinfection.

scholarly journals P53 and The Immune Response: 40 Years of Exploration—A Plan for the Future

2020 ◽  
Vol 21 (2) ◽  
pp. 541 ◽  
Author(s):  
Arnold J. Levine
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune System ◽  
P53 Protein ◽  
P53 Gene ◽  
T Cell Response ◽  
Innate Immune ◽  
Transplantation Antigen ◽  
Mutant Form ◽  
The Future

The p53 field was born from a marriage of the techniques of cancer virus research and immunology. Over the past 40 years, it has followed the path of cancer research. Now cancer treatments are turning to immunotherapy, and there are many hints of the role of the p53 protein in both the regulation of the innate immune system and as an antigen in adaptive immune responses. The p53 gene and protein are part of the innate immune system, and play an important role in infectious diseases, senescence, aging, and the surveillance of repetitive DNA and RNAs. The mutant form of the p53 protein in cancers elicits both a B-cell antibody response (a tumor antigen) and a CD-8 killer T-cell response (a tumor-specific transplantation antigen). The future will take the p53-immune response field of research into cancer immunotherapy, autoimmunity, inflammatory responses, neuro-degeneration, aging, and life span, and the regulation of epigenetic stability and tissue regeneration. The next 40 years will bring the p53 gene and its proteins out of a cancer focus and into an organismic and environmental focus.

scholarly journals Analyzing 24-Hour Blood Pressure Measurements with a Novel Cuffless Pulse Transit Time Device in Clinical Practice—Does the Software for Heartbeat Detection Matter?

Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 361
Author(s):  
Leo Kilian ◽  
Philipp Krisai ◽  
Thenral Socrates ◽  
Christian Arranto ◽  
Otmar Pfister ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Transit Time ◽  
Pulse Transit Time ◽  
Population Level ◽  
Raw Data ◽  
Invasive Blood Pressure ◽  
Individual Level ◽  
Non Invasive ◽  
The Individual ◽  
The Impact

Background: The Somnotouch-Non-Invasive-Blood-Pressure (NIBP) device delivers raw data consisting of electrocardiography and photoplethysmography for estimating blood pressure (BP) over 24 h using pulse-transit-time. The study’s aim was to analyze the impact on 24-hour BP results when processing raw data by two different software solutions delivered with the device. Methods: We used data from 234 participants. The Somnotouch-NIBP measurements were analyzed using the Domino-light and Schiller software and compared. BP values differing >5 mmHg were regarded as relevant and explored for their impact on BP classification (normotension vs. hypertension). Results: Mean (±standard deviation) absolute systolic/diastolic differences for 24-hour mean BP were 1.5 (±1.7)/1.1 (±1.3) mm Hg. Besides awake systolic BP (p = 0.022), there were no statistically significant differences in systolic/diastolic 24-hour mean, awake, and asleep BP. Twenty four-hour mean BP agreement (number (%)) between the software solutions within 5, 10, and 15 mmHg were 222 (94.8%), 231 (98.7%), 234 (100%) for systolic and 228 (97.4%), 232 (99.1%), 233 (99.5%) for diastolic measurements, respectively. A BP difference of >5 mmHg was present in 24 (10.3%) participants leading to discordant classification in 4–17%. Conclusion: By comparing the two software solutions, differences in BP are negligible at the population level. However, at the individual level there are, in a minority of cases, differences that lead to different BP classifications, which can influence the therapeutic decision.

scholarly journals The innate immune system and neurogenesis as modulating mechanisms of electroconvulsive therapy in pre-clinical studies

2020 ◽  
Vol 34 (10) ◽  
pp. 1086-1097
Author(s):  
Juliette Giacobbe ◽  
Carmine M Pariante ◽  
Alessandra Borsini
Keyword(s):  
Cell Proliferation ◽  
Immune System ◽  
Electroconvulsive Therapy ◽  
Clinical Studies ◽  
Innate Immune System ◽  
Innate Immune ◽  
System Response ◽  
Treatment Resistant ◽  
The Impact ◽  
Over Time

Background: Electroconvulsive therapy (ECT) is a powerful and fast-acting anti-depressant strategy, often used in treatment-resistant patients. In turn, patients with treatment-resistant depression often present an increased inflammatory response. The impact of ECT on several pathophysiological mechanisms of depression has been investigated, with a focus which has largely been on cellular and synaptic plasticity. Although changes in the immune system are known to influence neurogenesis, these processes have principally been explored independently from each other in the context of ECT. Objective: The aim of this review was to compare the time-dependent consequences of acute and chronic ECT on concomitant innate immune system and neurogenesis-related outcomes measured in the central nervous system in pre-clinical studies. Results: During the few hours following acute electroconvulsive shock (ECS), the expression of the astrocytic reactivity marker glial fibrillary acidic protein (GFAP) and inflammatory genes, such as cyclooxygenase-2 (COX2), were significantly increased together with the neurogenic brain-derived neurotrophic factor (BDNF) and cell proliferation. Similarly, chronic ECS caused an initial upregulation of the same astrocytic marker, immune genes, and neurogenic factors. Interestingly, over time, inflammation appeared to be dampened, while glial activation and neurogenesis were maintained, after either acute or chronic ECS. Conclusion: Regardless of treatment duration ECS would seemingly trigger a rapid increase in inflammatory molecules, dampened over time, as well as a long-lasting activation of astrocytes and production of growth and neurotrophic factors, leading to cell proliferation. This suggests that both innate immune system response and neurogenesis might contribute to the efficacy of ECT.

Effect of plinabulin, a novel late-clinical stage immunotherapeutic agent on the adaptive and innate immune system.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 8-8
Author(s):  
Ramon W. Mohanlal ◽  
Lan Huang
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Clinical Stage ◽  
Onset Time ◽  
Immune Defense ◽  
Innate Immune ◽  
Dependent Manner ◽  
Breast Cancer Patients ◽  
Post Dose ◽  
The Impact

8 Background: Plinabulin (Plin) is a small molecule Dendritic Cell modulator, which in the presence of antigen, increases T-cell proliferation in an antigen-dependent manner marrow. The addition of Plin to Docetaxel (Doc) improved mOS with 4.6 months vs Docetaxel monotherapy, and prolonged DoR with more than 1 year (p < 0.05), which is indicative of an immune-mediated mechanism of action (Mohanlal, ASCO-SITC 2017). Neutrophils are our first line of innate immune defense against foreign invaders. We previously reported that Plinabulin prevents chemotherapy (Chemo) Induced Neutropenia (CIN) in patients receiving Doc or TAC throughout the cycle (Doc, Doxorubicin, Cyclophosphamide) (Blayney ASH 2018, St Gallen 2019). Here we analyzed the onset time of neutrophil increase following Plin administration. In addition, we analyzed the impact of Plin on plasma haptoglobin, which is an acute phase protein with anti-inflammatory effects together with immune-enhancing effects and is an integral part of innate immunity (Kristiansen Nature 2001). Methods: Absolute neutrophil count (ANC) and haptoglobin data were analyzed from Phase 2 study BPI-2358-106 (NCT03294577) with 10 (n = 15), 20 (n = 15) and 30 mg/m2 (n = 12) Plin in Breast Cancer patients receiving TAC. Plin was administered on Day 1. ANC and Haptoglobin were analyzed by a Central Laboratory (Covance), from blood draws at predose, and post-dose Plin at Day 2,3,6,7,8,9,10,11,12,13 and 15, and changes relative to predose value were evaluated. Results: Plin dose-dependently increased ANC within 1 day (P < 0.001) and Haptoglobin within 3 days (P < 0.03) of dosing. Mean haptoglobin (P < 0.0005) and ANC (P < 0.001) levels increased with ~two-fold vs baseline levels. ANC levels remained increased for approximately 1 week and haptoglobin levels for > 3 weeks. Conclusions: Based on Plinabulin’s ability to stimulate the innate system, together with its previously reported evidence as a potent activator of the adaptive immune system (Mohanlal, ASCO-SITC 2017), it is concluded that Plinabulin is a potent stimulator of the adaptive and innate immune system. Clinical trial information: NCT03294577.

scholarly journals The Impact of Lactobacillus casei on the Composition of the Cecal Microbiota and Innate Immune System Is Strain Specific

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0156374 ◽  
Author(s):  
Busra Aktas ◽  
Travis J. De Wolfe ◽  
Nasia Safdar ◽  
Benjamin J. Darien ◽  
James L. Steele
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Lactobacillus Casei ◽  
Innate Immune ◽  
Cecal Microbiota ◽  
The Impact ◽  
Is Strain

scholarly journals Insights into Innate Immune Response Against SARS-CoV-2 Infection

2021 ◽  
Vol 29 (3) ◽  
pp. 255-269
Author(s):  
Adina Huțanu ◽  
Anca Meda Georgescu ◽  
Akos Vince Andrejkovits ◽  
William Au ◽  
Minodora Dobreanu
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Innate Immune System ◽  
Time Course ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Interferon Response ◽  
Humoral Factors ◽  
Key Steps

Abstract The innate immune system is mandatory for the activation of antiviral host defense and eradication of the infection. In this regard, dendritic cells, natural killer cells, macrophages, neutrophils representing the cellular component, and cytokines, interferons, complement or Toll-Like Receptors, representing the mediators of unspecific response act together for both activation of the adaptive immune response and viral clearance. Of great importance is the proper functioning of the innate immune response from the very beginning. For instance, in the early stages of viral infection, the defective interferon response leads to uncontrolled viral replication and pathogen evasion, while hypersecretion during the later stages of infection generates hyperinflammation. This cascade activation of systemic inflammation culminates with cytokine storm syndrome and hypercoagulability state, due to a close interconnection between them. Thus an unbalanced reaction, either under- or over- stimulation of the innate immune system will lead to an uncoordinated response and unfavorable disease outcomes. Since both cellular and humoral factors are involved in the time-course of the innate immune response, in this review we aimed to address their gradual involvement in the antiviral response with emphasis on key steps in SARS-CoV-2 infection.

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