scholarly journals COVID-19 immunologic and toxicological implication: Innate immune sensor and immune escape

2021 ◽  
Vol 5 (1) ◽  
pp. 001-017
Author(s):  
M Luisetto ◽  
Ilman Ahnaf ◽  
Khan Farhan Ahmad ◽  
Edbey Khaled ◽  
Hamid Gamal Abdul ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Escape ◽  
Severe Disease ◽  
Point Of View ◽  
Innate Immune ◽  
Severe Condition ◽  
New Variant ◽  
Rapid Emergence ◽  
New Strategies ◽  
Viral Respiratory

Related COVID-19 and new Variant and treatment like vaccine it is relevant to deeply verify the immunologic implication and in a special way regarding the innate immune sensor system and the evasion of the immune system. This can be crucial to search for new strategies to fight this severe disease under a Toxicology-antidotes point of view. The rapid emergence of a new variant is under study by researchers because some of these show different responses to antibodies as reported in literature (vaccine efficacy?). In this article after a review part it is submitted a collection of hypothesis of solution to contrast COVID-19. Spread and mortality and project hypothesis. A new toxicological approach also in a viral respiratory disease can be a novelty to adequately fight this severe condition and this focusing not only towards specific immunity but also a specific measures. A toxicological approach in drug- vaccine like products designing makes it possible to get the clinical outcomes needed.

scholarly journals N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2

2021 ◽  
Author(s):  
Christopher M Weiss ◽  
Hongwei Liu ◽  
Erin E Ball ◽  
Samuel Lam ◽  
Tomas Hode ◽  
...  
Keyword(s):  
Immune Responses ◽  
Infectious Virus ◽  
Severe Disease ◽  
Upper Airway ◽  
Innate Immune ◽  
Morbidity And Mortality ◽  
Vaccine Hesitancy ◽  
Innate Immune Responses ◽  
Before And After ◽  
Rapid Emergence

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in more than 4 million deaths in the 20 months since the virus was discovered. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout and vaccine hesitancy. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N-dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of β-0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans. We tested GC as a potential countermeasure for COVID-19. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway and lungs. Our findings demonstrate a new application for soluble immunoadjuvants like GC for preventing severe disease associated with SARS-CoV-2.

scholarly journals Leptospiral LPS escapes mouse TLR4 internalization and TRIF-associated antimicrobial responses through O antigen and associated lipoproteins

2020 ◽  
Author(s):  
Delphine Bonhomme ◽  
Ignacio Santecchia ◽  
Frédérique Vernel-Pauillac ◽  
Martine Caroff ◽  
Pierre Germon ◽  
...  
Keyword(s):  
Immune Escape ◽  
Severe Disease ◽  
Bacterial Pathogen ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Escape Mechanism ◽  
O Antigen ◽  
Molecular Patterns ◽  
Dependent Pathway

AbstractLeptospirosis is a worldwide re-emerging zoonosis caused by pathogenic Leptospira spp. All vertebrate species can be infected; humans are sensitive hosts whereas other species, such as rodents, may become long-term renal carrier reservoirs. Upon infection, innate immune responses are initiated by recognition of Microbial Associated Molecular Patterns (MAMPs) by Pattern Recognition Receptors (PRRs). Among MAMPs, the lipopolysaccharide (LPS) is recognized by the Toll-Like-Receptor 4 (TLR4) and activates both the MyD88-dependent pathway at the plasma membrane and the TRIF-dependent pathway after TLR4 internalization. We previously showed that leptospiral LPS is not recognized by the human TLR4, whereas it signals through murine TLR4, which mediates mouse resistance to acute leptospirosis. However, leptospiral LPS has low endotoxicity in mouse cells and is an agonist of TLR2, the sensor for bacterial lipoproteins. Here, using confocal microscopy and flow cytometry, we showed that the LPS of L. interrogans did not induce internalization of TLR4 in mouse macrophages, unlike the LPS of Escherichia coli. Consequently, the LPS failed to induce the production of the TRIF-dependent nitric oxide and RANTES, both important antimicrobial responses. Using shorter O antigen LPS and repurified leptospiral LPS with reporter HEK cells, we further found this TLR4-TRIF escape to be dependent on both the co-purifying lipoproteins and the full-length O antigen. Furthermore, our data suggest that the O antigen could alter the binding of the leptospiral LPS to the co-receptor CD14 that is essential for TLR4-TRIF activation. Overall, we describe here a novel immune escape mechanism linked to leptospiral LPS. We hypothesize that the LPS, already known as a virulence factor, plays a major role in the innate immune evasion of the leptospires, thereby contributing to their stealthiness and chronicity in mice.Author summaryLeptospira interrogans is a bacterial pathogen, responsible for leptospirosis, a worldwide neglected reemerging disease. L. interrogans may cause an acute severe disease in humans, whereas rodents and other animals asymptomatically carry the leptospires in their kidneys. They can therefore excrete live bacteria in urine and contaminate the environment. Leptospires are stealth pathogens known to escape the innate immune defenses of their hosts. They are covered in lipopolysaccharide (LPS), a bacterial motif recognized in mammals through the Toll-like receptor 4 (TLR4), which triggers two different signaling pathways. We showed previously that pathogenic leptospires escape TLR4 recognition in humans. Here we show in mice that the leptospiral LPS triggers only one arm of the TLR4 pathway and escapes the other, hence avoiding production of antimicrobial compounds. Removing the lipoproteins that always co-purify with the leptospiral LPS, or using shorter LPS, restores the stimulation of both pathways. This suggests a novel escape mechanism linked to the LPS and involving lipoproteins that could be instrumental for leptospires to escape the mouse defense and allows for their chronic renal colonization.

scholarly journals Three SARS-CoV-2 reinfection cases by the new Variant of Concern (VOC) P.1/501Y.V3

2021 ◽  
Author(s):  
Felipe Naveca ◽  
Cristiano da Costa ◽  
Valdinete Nascimento ◽  
Victor Souza ◽  
André Corado ◽  
...  
Keyword(s):  
Immune Escape ◽  
Severe Disease ◽  
Genomic Analysis ◽  
Severe Illness ◽  
Infection Event ◽  
New Variant ◽  
Recent Emergence ◽  
Potential Impact ◽  
Amazonas State ◽  
Generation Sequencing

Abstract The SARS-CoV-2 lineage B.1.1.28 has been evolving in Brazil since February 2020 giving origin to multiple local clades including the new Variant of Concern (VOC) designated P.1 or 501Y.V3. The recent emergence of sub-lineages with convergent mutations in the spike (S) protein raises concern about the potential impact on viral infectivity and immune escape. We describe here the first three confirmed SARS-CoV-2 reinfections cases with the new VOC P.1 in residents of the Amazonas state, Brazil. Three female patients, 29, 40, and 50-year-old, were RT-PCR confirmed for SARS-CoV-2 on two occasions, with at least 92 days apart. Next-generation sequencing and phylogenetic analysis were conducted to precisely access the SARS-CoV-2 lineages of each infection event. SARS-CoV-2 genomic analysis confirmed three cases of reinfections caused by the VOC P.1 in patients that were primo-infected by distinct viral lineages 3–9 months earlier. Case 1 (29-year-old) was positive on March 24, 2020 (lineage B.1.195) and then on December 30, 2020 (lineage P.1); case 2 (50-year-old) was positive on October 19, 2020 (lineage B.1.1.33) and on January 19, 2021 (lineage P.1); case 3 (40-year-old) was positive on April 22, 2020 (lineage B.1.195) and on January 29, 2021 (lineage P.1). The three patients displayed low mean Ct values (< 22) at nasopharyngeal samples and reported less severe illness during reinfection. The present study provides the first evidence of the new VOC P.1 causing multiple reinfections during the second epidemic peak in the Amazonas state. Our findings suggest that reinfected individuals may have been infectious. Although immune responses induced by natural infections do not necessarily prevent subsequent infections by the VOC P.1, they may still protect from severe disease.

scholarly journals Tools and Drugs for Purine-Binding Targets—Important Players in Inflammation and Cancer

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 33
Author(s):  
Christa E. Müller
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Escape ◽  
Gold Rush ◽  
Innate Immune ◽  
Receptor Subtypes ◽  
Cancer Cell Proliferation ◽  
A2b Receptor ◽  
Cancer Tissues ◽  
Adenosine A2a

Despite decades of research, only few drugs have been approved that interact with purine receptors. Recently, new hypes and hopes have been created in the field, mainly due to the gold rush fever in immuno-oncology. Adenosine is one of the strongest immunosuppressant agents of the innate immune system. Cancer cells and tissues can release large amounts of ATP, which is immediately hydrolyzed by ectonucleotidases. These ecto-enzymes, including ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1, CD203a), ectonucleoside diphospho­hydrolase 1 (NTPDase1, CD39), and ecto-5′-nucleotidase (CD73), are upregulated on many cancer cells, leading to the production of adenosine. The cloud of adenosine formed around cancer tissues contributes to immune escape by interacting with adenosine A2A and A2B receptor subtypes (A2AAR, A2BAR) on immune cells. In addition, activation of A2BARs by adenosine enhances cancer cell proliferation, metastasis, and angiogenesis. Blockade of A2A and A2B adenosine receptors and/or inhibition of adenosine formation by blocking ectonucleotidases are being pursued as novel principles that activate the immune system to defeat cancer. Recent progress in the development of adenosine receptor antagonists and ectonucleotidase inhibitors will be presented and discussed.

scholarly journals The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Sara Gabrielli ◽  
Claudio Ortolani ◽  
Genny del Zotto ◽  
Francesca Luchetti ◽  
Barbara Canonico ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Point Of View ◽  
Innate Immune ◽  
Adaptive Immune ◽  
System A ◽  
Evolutionary Point

Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.

scholarly journals The Role of the Innate Immune System in Cancer Dormancy and Relapse

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5621
Author(s):  
Noah M. Chernosky ◽  
Ilaria Tamagno
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Innate Immune System ◽  
Immune Escape ◽  
Disease Process ◽  
Innate Immune ◽  
Cancer Dormancy

Metastatic spread and recurrence are intimately linked to therapy failure, which remains an overarching clinical challenge for patients with cancer. Cancer cells often disseminate early in the disease process and can remain dormant for years or decades before re-emerging as metastatic disease, often after successful treatment. The interactions of dormant cancer cells and their metastatic niche, comprised of various stromal and immune cells, can determine the length of time that cancer cells remain dormant, as well as when they reactivate. New studies are defining how innate immune cells in the primary tumor may be corrupted to help facilitate many aspects of dissemination and re-emergence from a dormant state. Although the scientific literature has partially shed light on the drivers of immune escape in cancer, the specific mechanisms regulating metastasis and dormancy in the context of anti-tumor immunity are still mostly unknown. This review follows the journey of metastatic cells from dissemination to dormancy and the onset of metastatic outgrowth and recurrent tumor development, with emphasis on the role of the innate immune system. To this end, further research identifying how immune cells interact with cancer cells at each step of cancer progression will pave the way for new therapies that target the reactivation of dormant cancer cells into recurrent, metastatic cancers.

Panic makes you more susceptible to covid-19 (Preprint)

2020 ◽  
Author(s):  
Md Musharraf Hossain ◽  
Colin R Dunstan
Keyword(s):  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Innate Immune System ◽  
Severe Disease ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Cytokine Storm ◽  
Adaptive Immune ◽  
Storm Response ◽  
Short Period

UNSTRUCTURED COVID-19 is the official name describing the coronavirus disease causing by the virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Its higher infection rate has led to worldwide spread making it a more dangerous threat than other coronavirus related diseases. As this virus spreads and responses from governments become more constraining of normal activities, we are seeing levels of anxiety among people increase over a relatively short period of time. When we are stressed the immune system’s ability to defend us from infections is reduced. Stress can suppress the innate immune system that provides the initial defence against viral infection making us more susceptible to Covid-19. In contrast, stress can cause overactivity of the adaptive immune system making a cytokine storm response leading to severe disease and death more likely. Management of stress levels has become an important strategy to reduce the risks of COVID-19.

The immunologic response to severe acute respiratory syndrome coronavirus 2

2021 ◽  
Vol 42 (6) ◽  
pp. 495-505
Author(s):  
Nicole K. Le ◽  
Kelsey Kaman ◽  
Hannah C. Martin ◽  
Jyotsna Mullur ◽  
Kristen K. Stenehjem ◽  
...  
Keyword(s):  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Severe Disease ◽  
Significant Proportion ◽  
Molecular Techniques ◽  
Innate Immune ◽  
Immunologic Response ◽  
Human Immune System ◽  
Diagnostic Strategies ◽  
Human Immune

Background: The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated the worst global pandemic in a century, which has caused millions of infections and deaths as well as massive economic repercussions. Objective: As with any pathogenic virus, it is crucial to understand its unique interactions with the human immune system so that pharmaceutical and prophylactic interventions can be deployed to effectively control the pandemic. Methods: A literature search by using PubMed was conducted in 2020 with variants of the terms “COVID-19,” “SARS-CoV-2,” and “immunological response.” English language articles that presented original data about the immunologic response to coronavirus disease 2019 (COVID-19) were selected for review. This article reviewed the current understanding of the innate and adaptive immune responses to SARS-CoV-2 infection, including their relationship to current therapeutic and diagnostic strategies. Results: SARS-CoV-2 uses several unique molecular techniques to evade detection by the innate immune system early in the course of infection, and upregulation of these innate immune pathways may possibly accelerate the time to recovery and prevent severe disease. Although the majority of cases results in the patients' recovery, a significant proportion of infections result in deaths prompted by the host's inflammatory overreaction to the infection, a response that can be attenuated with corticosteroids and potentially other immune modulators. Conclusion: Current work by the scientific community to further understand how SARS-CoV-2 interacts with the human immune system will be invaluable to our response and preparedness for future coronavirus pandemics.

scholarly journals CD47 suppresses phagocytosis by repositioning SIRPA and preventing integrin activation

2019 ◽  
Author(s):  
Meghan A. Morrissey ◽  
Ronald D. Vale
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Innate Immune System ◽  
Chemical Activation ◽  
Innate Immune ◽  
Integrin Activation ◽  
Signaling Axis ◽  
Potential Applications ◽  
Inhibitory Signaling ◽  
New Strategies

SummaryMacrophages must engulf dead cells, debris, and pathogens, while selecting against healthy cells to prevent autoimmunity. Healthy cells express CD47 on their surface, which activates the SIRPA receptor on macrophages to suppress engulfment. Cancer cells overexpress CD47 to evade clearance by the innate immune system, making the CD47-SIRPA signaling axis an appealing therapeutic target. However, the mechanism by which CD47-SIRPA inhibits engulfment remains poorly understood. Here, we dissect SIRPA signaling using a reconstituted target with varying concentrations of activating and inhibitor ligands. We find that SIRPA is excluded from the phagocytic synapse between the macrophage and its target unless CD47 is present. Artificially directing SIRPA to the kinase-rich synapse in the absence of CD47 activates SIRPA and suppresses engulfment, indicating that the localization of the receptor is critical for inhibitory signaling. CD47-SIRPA inhibits integrin activation in the macrophage, reducing macrophage-target contact and suppressing phagocytosis. Chemical activation of integrins can override this effect and drive engulfment of CD47-positive targets, including cancer cells. These results suggest new strategies for overcoming CD47-SIRPA inhibition of phagocytosis with potential applications in cancer immunotherapy.

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