scholarly journals Molecular Insights of Immune Responses Variability in COVID-19 Patients: A Review

2021 ◽  
Vol 10 (3) ◽  
pp. 2402-2413
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Inflammatory Response ◽  
Clinical Symptoms ◽  
Multiorgan Failure ◽  
Innate Immune ◽  
Immune Memory ◽  
System Response ◽  
The Difference ◽  
Novel Coronavirus

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.

scholarly journals MiR-146b Mediates Endotoxin Tolerance in Human Phagocytes

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Tiziana Ada Renzi ◽  
Marcello Rubino ◽  
Laura Gornati ◽  
Cecilia Garlanda ◽  
Massimo Locati ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Inflammatory Response ◽  
Innate Immune Response ◽  
Endotoxin Tolerance ◽  
Innate Immune ◽  
Human Monocytes ◽  
Key Factors ◽  
Tlr Signaling ◽  
Tolerant State

A proper regulation of the innate immune response is fundamental to keep the immune system in check and avoid a chronic status of inflammation. As they act as negative modulators of TLR signaling pathways, miRNAs have been recently involved in the control of the inflammatory response. However, their role in the context of endotoxin tolerance is just beginning to be explored. We here show that miR-146b is upregulated in human monocytes tolerized by LPS, IL-10, or TGFβpriming and demonstrate that its transcription is driven by STAT3 and RUNX3, key factors downstream of IL-10 and TGFβsignaling. Our study also found that IFNγ, known to revert LPS tolerant state, inhibits miR-146b expression. Finally, we provide evidence that miR-146b levels have a profound effect on the tolerant state, thus candidating miR-146b as a molecular mediator of endotoxin tolerance.

scholarly journals TRINITY OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS-2: ORIGIN, GENOTYPE, PHENOTYPE, AND IMMUNE RESPONSE IN CORONAVIRUS DISEASE-2019

2021 ◽  
pp. 28-36
Author(s):  
MURUGAN NANDAGOPAL ◽  
ARULMOZHI BALAKRISHNAN ◽  
CHIRAYU PADHIAR
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Innate Immune System ◽  
Clinical Symptoms ◽  
Innate Immune ◽  
Host Immune System ◽  
Wide Range ◽  
Novel Coronavirus ◽  
Classification Structure

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.

scholarly journals Determining controllability of sepsis using genetic algorithms on a proxy agent-based model of systemic inflammation

2017 ◽  
Author(s):  
Chase Cockrell ◽  
Gary An
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Mortality Rate ◽  
Inflammatory Response ◽  
Disease Process ◽  
The United States ◽  
Innate Immune ◽  
Agent Based ◽  
Human Immune ◽  
Inflammatory Response To Injury

AbstractSepsis, a manifestation of the body’s inflammatory response to injury and infection, has a mortality rate of between 28%-50% and affects approximately 1 million patients annually in the United States. Currently, there are no therapies targeting the cellular/molecular processes driving sepsis that have demonstrated the ability to control this disease process in the clinical setting. We propose that this is in great part due to the considerable heterogeneity of the clinical trajectories that constitute clinical “sepsis,” and that determining how this system can be controlled back into a state of health requires the application of concepts drawn from the field of dynamical systems. In this work, we consider the human immune system to be a random dynamical system, and investigate its potential controllability using an agent-based model of the innate immune response (the Innate Immune Response ABM or IIRABM) as a surrogate, proxy system. Simulation experiments with the IIRABM provide an explanation as to why single/limited cytokine perturbations at a single, or small number of, time points is unlikely to significantly improve the mortality rate of sepsis. We then use genetic algorithms (GA) to explore and characterize multi-targeted control strategies for the random dynamical immune system that guide it from a persistent, non-recovering inflammatory state (functionally equivalent to the clinical states of systemic inflammatory response syndrome (SIRS) or sepsis) to a state of health. We train the GA on a single parameter set with multiple stochastic replicates, and show that while the calculated results show good generalizability, more advanced strategies are needed to achieve the goal of adaptive personalized medicine. This work evaluating the extent of interventions needed to control a simplified surrogate model of sepsis provides insight into the scope of the clinical challenge, and can serve as a guide on the path towards true “precision control” of sepsis.Author summarySepsis, characterized by the body’s inflammatory response to injury and infection, has a mortality rate of between 28%-50% and affects approximately 1 million patients annually in the United States. Currently, there are no therapies targeting the cellular/molecular processes driving sepsis that have demonstrated the ability to control this disease process. In this work, we utilize a computational model of the human immune response to infectious injury to offer an explanation as to why previously attempted treatment strategies are inadequate and why the current approach to drug/therapy-development is inadequate. We then use evolutionary computation algorithms to explore drug-intervention space using this same computational model. This allows us to characterize the scale and scope of interventions needed to successfully control sepsis, as well as the types of data needed to derive these interventions. We demonstrate that multi-point and time-dependent varying controls are necessary and able to control the cytokine network dynamics of the immune system.

Boosting innate immunity during SARS-CoV-2 clearance

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Abhishesh Kumar Mehata ◽  
Deepa Dehari ◽  
Anuj Kumar Mehta ◽  
Alim Miya
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Immune System ◽  
Innate Immune ◽  
Cell Immune Response ◽  
Current Scenario ◽  
Pathogenic Viruses ◽  
Immune Check Points ◽  
Novel Coronavirus ◽  
The Individual

: 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.

scholarly journals An innate immune activation state prior to vaccination predicts responsiveness to multiple vaccines

2021 ◽  
Author(s):  
Slim Fourati ◽  
Lewis E Tomalin ◽  
Matthew P Mulè ◽  
Daniel G Chawla ◽  
Bram Gerritsen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Inflammatory Response ◽  
Antibody Response ◽  
Immune Cell ◽  
Serum Antibody ◽  
Cell Subset ◽  
Innate Immune ◽  
Myeloid Dendritic Cells ◽  
Human Immunology

Many factors determine whether an individual responding to vaccination will generate an immune response that can lead to protection. Several studies have shown that the pre-vaccination immune state associate with the antibody response to vaccines. However, the generalizability and mechanisms that underlie this association remain poorly defined. Here, we sought to identify a common pre-vaccination signature and mechanisms that could predict the immune response across a wide variety of vaccines. We leveraged the "Immune Signatures Data Resource" created by the NIH Human Immunology Project Consortium (HIPC) to integrate data from 28 studies involving 13 different vaccines and associate the blood transcriptional status of 820 healthy young adults with their responses. An unsupervised analysis of blood transcriptional profiles across studies revealed three distinct pre-vaccination states, characterized by the differential expression of genes associated with a pro-inflammatory response, cell proliferation, and metabolism alterations downstream of NFκB and IRF7. Innate and adaptive immune cell subset-specific genes were also associated with the three pre-vaccination states. Importantly, individuals whose pre-vaccination state was enriched in pro-inflammatory response genes known to be downstream of NFκB tended to have higher serum antibody responses one month after vaccination. A supervised analysis of the same data resulted in a single classifier, also enriched for NFκB regulated genes, that predicted the antibody response across most of the vaccines. Projection into single-cell RNA-sequencing data suggested that this pre-vaccination state was attributable to the signature of activation of non-classical monocytes and myeloid dendritic cells. Transcriptional signatures of recent exposure to bacterial and not viral infections were enriched in the high pro-inflammatory pre-vaccination state and also included NFκB regulated genes. The pro-inflammatory pre-vaccination state was highly reminiscent of the innate activation state triggered by TLR ligands or adjuvants. These results demonstrate that wide variations in the transcriptional state of the immune system in humans can be a key determinant of responsiveness to vaccination. They also define a transcriptional signature NFκB activation at baseline, that is associated with a greater magnitude of antibody response to 13 different vaccines, and suggest that modulation of the innate immune system by next-generation adjuvants targeting NFκB before vaccine administration may improve vaccine responsiveness.

scholarly journals Modeling Virus-Induced Inflammation in Zebrafish: A Balance Between Infection Control and Excessive Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Con Sullivan ◽  
Brandy-Lee Soos ◽  
Paul J. Millard ◽  
Carol H. Kim ◽  
Benjamin L. King
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Inflammatory Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Innate Immune System ◽  
Innate Immune ◽  
Zebrafish Model ◽  
Infection Models

The inflammatory response to viral infection in humans is a dynamic process with complex cell interactions that are governed by the immune system and influenced by both host and viral factors. Due to this complexity, the relative contributions of the virus and host factors are best studied in vivo using animal models. In this review, we describe how the zebrafish (Danio rerio) has been used as a powerful model to study host-virus interactions and inflammation by combining robust forward and reverse genetic tools with in vivo imaging of transparent embryos and larvae. The innate immune system has an essential role in the initial inflammatory response to viral infection. Focused studies of the innate immune response to viral infection are possible using the zebrafish model as there is a 4-6 week timeframe during development where they have a functional innate immune system dominated by neutrophils and macrophages. During this timeframe, zebrafish lack a functional adaptive immune system, so it is possible to study the innate immune response in isolation. Sequencing of the zebrafish genome has revealed significant genetic conservation with the human genome, and multiple studies have revealed both functional conservation of genes, including those critical to host cell infection and host cell inflammatory response. In addition to studying several fish viruses, zebrafish infection models have been developed for several human viruses, including influenza A, noroviruses, chikungunya, Zika, dengue, herpes simplex virus type 1, Sindbis, and hepatitis C virus. The development of these diverse viral infection models, coupled with the inherent strengths of the zebrafish model, particularly as it relates to our understanding of macrophage and neutrophil biology, offers opportunities for far more intensive studies aimed at understanding conserved host responses to viral infection. In this context, we review aspects relating to the evolution of innate immunity, including the evolution of viral pattern recognition receptors, interferons and interferon receptors, and non-coding RNAs.

scholarly journals Secondary haemophagocytic lymphohistiocytosis in COVID-19: correlation of the autopsy findings of bone marrow haemophagocytosis with HScore

2021 ◽  
pp. jclinpath-2020-207337
Author(s):  
Claudia Núñez-Torrón ◽  
Ana Ferrer-Gómez ◽  
Esther Moreno Moreno ◽  
Belen Pérez-Mies ◽  
Jesús Villarrubia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Immune System ◽  
Multiorgan Failure ◽  
Histological Findings ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Bone Marrow Tissue ◽  
Autopsy Findings ◽  
Specific Finding ◽  
Clinical Records

BackgroundSecondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by a hyper activation of immune system that leads to multiorgan failure. It is suggested that excessive immune response in patients with COVID-19 could mimic this syndrome. Some COVID-19 autopsy studies have revealed the presence of haemophagocytosis images in bone marrow, raising the possibility, along with HScore parameters, of sHLH.AimOur objective is to ascertain the existence of sHLH in some patients with severe COVID-19.MethodsWe report the autopsy histological findings of 16 patients with COVID-19, focusing on the presence of haemophagocytosis in bone marrow, obtained from rib squeeze and integrating these findings with HScore parameters. CD68 immunohistochemical stains were used to highlight histiocytes and haemophagocytic cells. Clinical evolution and laboratory parameters of patients were collected from electronic clinical records.ResultsEleven patients (68.7%) displayed moderate histiocytic hyperplasia with haemophagocytosis (HHH) in bone marrow, three patients (18.7%) displayed severe HHH and the remainder were mild. All HScore parameters were collected in 10 patients (62.5%). Among the patients in which all parameters were evaluable, eight patients (80%) had an HScore >169. sHLH was not clinically suspected in any case.ConclusionsOur results support the recommendation of some authors to use the HScore in patients with severe COVID-19 in order to identify those who could benefit from immunosuppressive therapies. The presence of haemophagocytosis in bone marrow tissue, despite not being a specific finding, has proved to be a very useful tool in our study to identify these patients.

scholarly journals TIFA Signaling in Gastric Epithelial Cells Initiates the cag Type 4 Secretion System-Dependent Innate Immune Response to Helicobacter pylori Infection

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Alevtina Gall ◽  
Ryan G. Gaudet ◽  
Scott D. Gray-Owen ◽  
Nina R. Salama
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Secretion System ◽  
Innate Immune ◽  
Gastric Ulcers ◽  
Bacterial Clearance ◽  
Gastric Epithelial Cells ◽  
H Pylori

ABSTRACT Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, causing inflammation which, in some cases, leads to gastric ulcers and cancer. The clinical outcome of infection depends on a complex interplay of bacterial, host genetic, and environmental factors. Although H. pylori is recognized by both the innate and adaptive immune systems, this rarely results in bacterial clearance. Gastric epithelial cells are the first line of defense against H. pylori and alert the immune system to bacterial presence. Cytosolic delivery of proinflammatory bacterial factors through the cag type 4 secretion system ( cag -T4SS) has long been appreciated as the major mechanism by which gastric epithelial cells detect H. pylori . Classically attributed to the peptidoglycan sensor NOD1, recent work has highlighted the role of NOD1-independent pathways in detecting H. pylori ; however, the bacterial and host factors involved have remained unknown. Here, we show that bacterially derived heptose-1,7-bisphosphate (HBP), a metabolic precursor in lipopolysaccharide (LPS) biosynthesis, is delivered to the host cytosol through the cag -T4SS, where it activates the host tumor necrosis factor receptor-associated factor (TRAF)-interacting protein with forkhead-associated domain (TIFA)-dependent cytosolic surveillance pathway. This response, which is independent of NOD1, drives robust NF-κB-dependent inflammation within hours of infection and precedes NOD1 activation. We also found that the CagA toxin contributes to the NF-κB-driven response subsequent to TIFA and NOD1 activation. Taken together, our results indicate that the sequential activation of TIFA, NOD1, and CagA delivery drives the initial inflammatory response in gastric epithelial cells, orchestrating the subsequent recruitment of immune cells and leading to chronic gastritis. IMPORTANCE H. pylori is a globally prevalent cause of gastric and duodenal ulcers and cancer. H. pylori antibiotic resistance is rapidly increasing, and a vaccine remains elusive. The earliest immune response to H. pylori is initiated by gastric epithelial cells and sets the stage for the subsequent immunopathogenesis. This study revealed that host TIFA and H. pylori -derived HBP are critical effectors of innate immune signaling that account for much of the inflammatory response to H. pylori in gastric epithelial cells. HBP is delivered to the host cell via the cag -T4SS at a time point that precedes activation of the previously described NOD1 and CagA inflammatory pathways. Manipulation of the TIFA-driven immune response in the host and/or targeting of ADP-heptose biosynthesis enzymes in H. pylori may therefore provide novel strategies that may be therapeutically harnessed to achieve bacterial clearance.

scholarly journals Tumour viruses and innate immunity

2017 ◽  
Vol 372 (1732) ◽  
pp. 20160267 ◽  
Author(s):  
Sharon E. Hopcraft ◽  
Blossom Damania
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Host Cells ◽  
Oncogenic Viruses ◽  
Barr Virus ◽  
Human T Cell ◽  
Epstein Barr

Host cells sense viral infection through pattern recognition receptors (PRRs), which detect pathogen-associated molecular patterns (PAMPs) and stimulate an innate immune response. PRRs are localized to several different cellular compartments and are stimulated by viral proteins and nucleic acids. PRR activation initiates signal transduction events that ultimately result in an inflammatory response. Human tumour viruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein–Barr virus, human papillomavirus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus type 1 and Merkel cell polyomavirus, are detected by several different PRRs. These viruses engage in a variety of mechanisms to evade the innate immune response, including downregulating PRRs, inhibiting PRR signalling, and disrupting the activation of transcription factors critical for mediating the inflammatory response, among others. This review will describe tumour virus PAMPs and the PRRs responsible for detecting viral infection, PRR signalling pathways, and the mechanisms by which tumour viruses evade the host innate immune system. This article is part of the themed issue ‘Human oncogenic viruses’.

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