scholarly journals SARS-CoV-2: From Structure to Pathology, Host Immune Response and Therapeutic Management

2020 ◽  
Vol 8 (10) ◽  
pp. 1468
Author(s):  
Grigore Mihaescu ◽  
Mariana Carmen Chifiriuc ◽  
Ciprian Iliescu ◽  
Corneliu Ovidiu Vrancianu ◽  
Lia-Mara Ditu ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Vaccine Development ◽  
Host Immune Response ◽  
Physical Factors ◽  
Respiratory Pathogens ◽  
Inflammatory Conditions ◽  
Multiplication Cycle ◽  
Wide Range

Coronaviruses are large, enveloped viruses with a single-stranded RNA genome, infecting both humans and a wide range of wild and domestic animals. SARS-CoV-2, the agent of the COVID-19 pandemic, has 80% sequence homology with SARS-CoV-1 and 96–98% homology with coronaviruses isolated from bats. The spread of infection is favored by prolonged exposure to high densities of aerosols indoors. Current studies have shown that SARS-CoV-2 is much more stable than other coronaviruses and viral respiratory pathogens. The severe forms of infection are associated with several risk factors, including advanced age, metabolic syndrome, diabetes, obesity, chronic inflammatory or autoimmune disease, and other preexisting infectious diseases, all having in common the pre-existence of a pro-inflammatory condition. Consequently, it is essential to understand the relationship between the inflammatory process and the specific immune response in SARS-CoV-2 infection. In this review, we present a general characterization of the SARS-CoV-2 virus (origin, sensitivity to chemical and physical factors, multiplication cycle, genetic variability), the molecular mechanisms of COVID-19 pathology, the host immune response and discuss how the inflammatory conditions associated with different diseases could increase the risk of COVID-19. Last, but not least, we briefly review the SARS-CoV-2 diagnostics, pharmacology, and future approaches toward vaccine development.

Strategies for search of pharmacological drugs against SARS-CoV-2 on the base of studying the structural-genetic features of coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2

2020 ◽  
Vol 18 (4) ◽  
pp. 269-296
Author(s):  
Vladimir I. Vashchenko ◽  
Vladimir N. Vilyaninov ◽  
Petr D. Shabanov
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Vaccine Development ◽  
Inflammatory Responses ◽  
Host Immune Response ◽  
Medication Cost ◽  
Atypical Pneumonia ◽  
Therapeutic Approaches ◽  
Mathematical Methods ◽  
Coronavirus Infection

A sudden outbreak of COVID-19 caused by a novel coronavirus, SARS-CoV-2, in Wuhan, China in December 2019 quickly grew into a global pandemic, putting at risk not only the global healthcare system, but also the world economy. As the disease continues to spread rapidly, the development of prophylactic and therapeutic approaches is urgently required. Although some progress has been made in understanding the viral structure and invasion mechanism of coronaviruses that may cause severe cases of the syndrome, due to the limited understanding of the immune effects caused by SARS-CoV-2, it is difficult for us to prevent patients from developing acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), the major complications of coronavirus infection. Therefore, any potential treatments should focus not only on direct killing of coronaviruses and prevention strategies by vaccine development, but also on keeping in check the acute immune/inflammatory responses, resulting in ARDS and PF. In addition, potential treatments currently under clinical trials focusing on killing coronaviruses or on developing vaccines preventing coronavirus infection largely ignore the host immune response. However, taking care of SARS-CoV-2 infected patients with ARDS and PF is considered to be the major difficulty. Therefore, further understanding of the host immune response to SARS-CoV-2 is extremely important for clinical resolution and saving medication cost. In addition to a breif overview of the structure, infection mechanism, and possible therapeutic approaches, we summarized and compared the hematopathologic effect and immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2. Also the basic molecular mechanisms of an atypical pneumonia and molecular targets SARS-CoV-2 that allows to allocate 8 basic directions of search of pharmacological agents for struggle with SARS-CoV-2 are discussed. Mathematical methods of search of perspective preparations for struggle with COVID-19 are in detail discussed. The pathophysiological mechanisms of an infection inducing a lymphopenia or cytokine storm that allows to allocate a special direction of search of pharmacological preparations for struggle against new coronaviruse SARS-CoV-2 are discussed.

scholarly journals Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

2020 ◽  
Vol 10 ◽  
Author(s):  
Marie-Noëlle Mévélec ◽  
Zineb Lakhrif ◽  
Isabelle Dimier-Poisson
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Vaccine Development ◽  
Host Immune Response ◽  
Oral Route ◽  
Effective Vaccine ◽  
Naked Dna ◽  
Protection Mechanisms ◽  
Immunogenic Proteins ◽  
Cellular Immune

Toxoplasmosis is a parasitic disease affecting human, livestock and cat. Prophylactic strategies would be ideal to prevent infection. In a One Health vaccination approach, the objectives would be the prevention of congenital disease in both women and livestock, prevention/reduction of T. gondii tissue cysts in food-producing animals; and oocyst shedding in cats. Over the last few years, an explosion of strategies for vaccine development, especially due to the development of genetic-engineering technologies has emerged. The field of vaccinology has been exploring safer vaccines by the generation of recombinant immunogenic proteins, naked DNA vaccines, and viral/bacterial recombinants vectors. These strategies based on single- or few antigens, are less efficacious than recombinant live-attenuated, mostly tachyzoite T. gondii vaccine candidates. Reflections on the development of an anti-Toxoplasma vaccine must focus not only on the appropriate route of administration, capable of inducing efficient immune response, but also on the choice of the antigen (s) of interest and the associated delivery systems. To answer these questions, the choice of the animal model is essential. If mice helped in understanding the protection mechanisms, the data obtained cannot be directly transposed to humans, livestock and cats. Moreover, effectiveness vaccines should elicit strong and protective humoral and cellular immune responses at both local and systemic levels against the different stages of the parasite. Finally, challenge protocols should use the oral route, major natural route of infection, either by feeding tissue cysts or oocysts from different T. gondii strains. Effective Toxoplasma vaccines depend on our understanding of the (1) protective host immune response during T. gondii invasion and infection in the different hosts, (2) manipulation and modulation of host immune response to ensure survival of the parasites able to evade and subvert host immunity, (3) molecular mechanisms that define specific stage development. This review presents an overview of the key limitations for the development of an effective vaccine and highlights the contributions made by recent studies on the mechanisms behind stage switching to offer interesting perspectives for vaccine development.

scholarly journals Lipophilicity of Bacteriochlorin-Based Photosensitizers as a Determinant for PDT Optimization through the Modulation of the Inflammatory Mediators

2019 ◽  
Vol 9 (1) ◽  
pp. 8 ◽  
Author(s):  
Barbara Pucelik ◽  
Luis G. Arnaut ◽  
Janusz M. Dąbrowski
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Near Infrared ◽  
Antitumor Immune Response ◽  
Infrared Light ◽  
Gm Csf ◽  
Hydrophobic Compound ◽  
Tnf Α ◽  
Wide Range

Photodynamic therapy (PDT) augments the host antitumor immune response, but the role of the PDT effect on the tumor microenvironment in dependence on the type of photosensitizer and/or therapeutic protocols has not been clearly elucidated. We employed three bacteriochlorins (F2BOH, F2BMet and Cl2BHep) of different polarity that absorb near-infrared light (NIR) and generated a large amount of reactive oxygen species (ROS) to compare the PDT efficacy after various drug-to-light intervals: 15 min. (V-PDT), 3h (E-PDT) and 72h (C-PDT). We also performed the analysis of the molecular mechanisms of PDT crucial for the generation of the long-lasting antitumor immune response. PDT-induced damage affected the integrity of the host tissue and developed acute (protocol-dependent) local inflammation, which in turn led to the infiltration of neutrophils and macrophages. In order to further confirm this hypothesis, a number of proteins in the plasma of PDT-treated mice were identified. Among a wide range of cytokines (IL-6, IL-10, IL-13, IL-15, TNF-α, GM-CSF), chemokines (KC, MCP-1, MIP1α, MIP1β, MIP2) and growth factors (VEGF) released after PDT, an important role was assigned to IL-6. PDT protocols optimized for studied bacteriochlorins led to a significant increase in the survival rate of BALB/c mice bearing CT26 tumors, but each photosensitizer (PS) was more or less potent, depending on the applied DLI (15 min, 3 h or 72 h). Hydrophilic (F2BOH) and amphiphilic (F2BMet) PSs were equally effective in V-PDT (>80 cure rate). F2BMet was the most efficient in E-PDT (DLI = 3h), leading to a cure of 65 % of the animals. Finally, the most powerful PS in the C-PDT (DLI = 72 h) regimen turned out to be the most hydrophobic compound (Cl2BHep), allowing 100 % of treated animals to be cured at a light dose of only 45 J/cm2.

Understanding the immune responses involved in mediating protection or immunopathology during leishmaniasis

2021 ◽  
Author(s):  
Thalia Pacheco-Fernandez ◽  
Greta Volpedo ◽  
Chaitenya Verma ◽  
Abhay R. Satoskar
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Public Health Problem ◽  
Host Immune Response ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Major Public Health Problem ◽  
Wide Range ◽  
Vector Borne ◽  
Leishmania Parasites

Leishmaniasis is a vector-borne Neglected Tropical Disease (NTD) transmitted by the sand fly and is a major public health problem worldwide. Infections caused by Leishmania clinically manifest as a wide range of diseases, such as cutaneous (CL), diffuse cutaneous (DCL), mucosal (MCL) and visceral leishmaniasis (VL). The host innate and adaptative immune responses play critical roles in the defense against leishmaniasis. However, Leishmania parasites also manipulate the host immune response for their survival and replication. In addition, other factors such as sand fly salivary proteins and microbiota also promote disease susceptibility and parasite spread by modulating local immune response. Thus, a complex interplay between parasite, sand fly and the host immunity governs disease severity and outcome. In this review, we discuss the host immune response during Leishmania infection and highlight the factors associated with resistance or susceptibility.

scholarly journals The Other Side of the Coin: Anti-inflammatory Antibody Therapy for Infectious Diseases

2019 ◽  
Vol 88 (2) ◽  
Author(s):  
David L. Goldman
Keyword(s):  
Immune Response ◽  
Antimicrobial Activity ◽  
Inflammatory Response ◽  
Infectious Diseases ◽  
Specific Antibody ◽  
Antibody Therapy ◽  
Host Immune Response ◽  
Antibody Activity ◽  
Viral Neutralization ◽  
Wide Range

ABSTRACT The inflammatory response to the fungus Pneumocystis jirovecii plays a central role in the respiratory failure associated with Pneumocystis pneumonia. To help ameliorate the inflammatory response, corticosteroids are used as an adjuvant to standard antimicrobial therapy. Corticosteroids, however, can have a wide range of effects (including deleterious effects) on the host immune response. To date, pathogen-specific antibody therapy has primarily been developed for both its direct antimicrobial activity (e.g., toxin and viral neutralization) and its ability to enhance the antimicrobial activity of the host immune response via effector cells, like macrophages and neutrophils. In this issue of Infection and Immunity, Hoy et al. (Z. Hoy, T. W. Wright, M. Elliott, J. Malone, et al., Infect Immun 88:e00640-19, 2020, https://doi.org/10.1128/IAI.00640-19) report on a surprising application of Pneumocystis-specific antibody therapy in treating disease by decreasing the inflammatory response. This effect appears to occur as a result of an enhanced phagocytic activity within the lung and an associated alteration in the macrophage phenotype. This study adds insight into our understanding of antibody activity and highlights the possibility of using antibody therapy to limit inflammation for other infectious diseases in which inflammatory damage plays a significant role in disease pathogenesis.

scholarly journals The Chairside Periodontal Diagnostic Toolkit: Past, Present, and Future

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 932
Author(s):  
Tae-Jun Ko ◽  
Kevin M. Byrd ◽  
Shin Ae Kim
Keyword(s):  
Immune Response ◽  
Technology Development ◽  
Periodontal Diseases ◽  
Host Immune Response ◽  
Disease Diagnosis ◽  
Non Invasive ◽  
Microbial Dysbiosis ◽  
Inflammatory Conditions ◽  
Research Initiatives

Periodontal diseases comprise a group of globally prevalent, chronic oral inflammatory conditions caused by microbial dysbiosis and the host immune response. These diseases specifically affect the tooth-supporting tissues (i.e., the periodontium) but are also known to contribute to systemic inflammation. If left untreated, periodontal diseases can ultimately progress to tooth loss, lead to compromised oral function, and negatively impact the overall quality of life. Therefore, it is important for the clinician to accurately diagnose these diseases both early and accurately chairside. Currently, the staging and grading of periodontal diseases are based on recording medical and dental histories, thorough oral examination, and multiple clinical and radiographic analyses of the periodontium. There have been numerous attempts to improve, automate, and digitize the collection of this information with varied success. Recent studies focused on the subgingival microbiome and the host immune response suggest there is an untapped potential for non-invasive oral sampling to assist clinicians in the chairside diagnosis and, potentially, prognosis. Here, we review the available toolkit available for diagnosing periodontal diseases, discuss commercially available options, and highlight the need for collaborative research initiatives and state-of-the-art technology development across disciplines to overcome the challenges of rapid periodontal disease diagnosis.

scholarly journals Steryl Glycosides in Fungal Pathogenesis: An Understudied Immunomodulatory Adjuvant

2020 ◽  
Vol 6 (1) ◽  
pp. 25 ◽  
Author(s):  
Tyler G. Normile ◽  
Kyle McEvoy ◽  
Maurizio Del Poeta
Keyword(s):  
Immune Response ◽  
Fungal Infections ◽  
Treatment Options ◽  
Host Immune Response ◽  
Novel Treatment ◽  
Wide Range ◽  
Efficacious Vaccine ◽  
Lipid Compounds ◽  
Fungal Interactions

Invasive fungal infections pose an increasing threat to human hosts, especially in immunocompromised individuals. In response to the increasing morbidity and mortality of fungal infections, numerous groups have shown great strides in uncovering novel treatment options and potential efficacious vaccine candidates for this increasing threat due to the increase in current antifungal resistance. Steryl glycosides are lipid compounds produced by a wide range of organisms, and are largely understudied in the field of pathogenicity, especially to fungal infections. Published works over the years have shown these compounds positively modulating the host immune response. Recent advances, most notably from our lab, have strongly indicated that steryl glycosides have high efficacy in protecting the host against lethal Cryptococcal infection through acting as an immunoadjuvant. This review will summarize the keystone studies on the role of steryl glycosides in the host immune response, as well as elucidate the remaining unknown characteristics and future perspectives of these compounds for the host–fungal interactions.

scholarly journals Identification of Sulfavant A as the First Synthetic TREM2 Ligand Discloses a Homeostatic Response of Dendritic Cells After Receptor Engagement

2022 ◽  
Author(s):  
Carmela Gallo ◽  
Emiliano Manzo ◽  
Giusi Barra ◽  
Laura Fioretto ◽  
Marcello Ziaco ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mhc Class Ii ◽  
Molecular Mechanisms ◽  
Vaccine Development ◽  
Class Ii ◽  
Receptor Activation ◽  
T Cell Response ◽  
Adjuvant Effect ◽  
Adjuvant Activity

Abstract The immune response arises from a fine balance of cellular and molecular mechanisms that provide for surveillance, tolerance, and elimination of dangers as pathogens. Improving the quality of the immune response remains a major goal in immunotherapy and vaccine development. Sulfavant A (SULF A) is a sulfolipid that has shown promising adjuvant activity in a cancer vaccine model. Here we report that SULF A is the first synthetic small molecule binding to the Triggering Receptor Expressed on Myeloid cells-2 (TREM2). The receptor engagement initiates an unconventional maturation of Dendritic cells (DCs) leading to upregulation of the Major Histocompatibility Complex class II (MHC Class II) and costimulatory molecules (CD83, CD86, DC54) without release of T helper type 1 (Th1) or 2 (Th2) cytokines. According to a TREM2 mechanism, this response is mediated by SYK-NFAT axis and is compromised by blockade and gene silencing of the receptor. Activation by SULF A preserved the DC functions to excite the allogeneic T cell response, and induced interleukin-10 (IL-10) release after lipopolysaccharide (LPS) stimulation. These results well support the adjuvant effect of SULF A and offer novel insights into the role of TREM2 in the differentiation of an unprecedented DC phenotype (homeDCs) that contributes to the maintenance of immune homeostasis without compromising lymphocyte activation and immunogenic response. The biological function of SULF-A may be of interest in various physiological and pathological processes involving the immune system.

scholarly journals Quantitative measurement of activity of JAK-STAT signaling pathways in blood samples and immune cells to predict innate and adaptive cellular immune response to viral infection and accelerate vaccine development

2020 ◽  
Author(s):  
Wilbert Bouwman ◽  
Wim Verhaegh ◽  
Laurent Holtzer ◽  
Anja van de Stolpe
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Signaling Pathways ◽  
Cellular Immune Response ◽  
Vaccine Development ◽  
Host Immune Response ◽  
Blood Samples ◽  
Pathway Activity ◽  
Adaptive Immune ◽  
Cellular Immune

AbstractThe host immune response determines the clinical course of a viral infection, for example in case of COVID-19 infection. The effectiveness of vaccination also depends on the induced immune response. Currently there is no method to measure the cellular immune response in blood samples. The functional activity of cells of innate and adaptive immune system is determined by coordinated activity of signaling pathways, especially the JAK-STAT pathways. Using a previously described approach we developed mRNA-based tests to measure activity of these signaling pathways, and show that they can be used to measure in a quantitative manner the cellular innate and adaptive immune response to a viral infection or vaccine in whole blood, PBMC, and specific immune cell type samples. Pathway activity level and range in healthy individuals was established, enabling interpretation of a pathway activity score on a patient sample without the need for a reference sample. Evidence is presented that the pathway activity analysis may also be useful for in vitro vaccine development and assessment of vaccine immunogenicity. Other envisioned applications lie in development of immunomodulatory drugs and drug response prediction and monitoring. Tests are expected to be of value in the COVID-19 crisis. In addition to the described Affymetrix microarray-based pathway tests for measuring host immune response, qPCR-based versions are in development; the latter can in principle be performed within three hours in routine hospital labs.

scholarly journals Molecular Mechanisms of Vitamin D-Mediated Immunomodulation

2021 ◽  
Vol 10 ◽  
pp. 2097
Author(s):  
Farhan Khashim Alswailmi ◽  
Syed Imran Ali Shah ◽  
Haleema Nawaz ◽  
Ghassab Mohammad Al-Mazaideh
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Molecular Mechanisms ◽  
Vitamin D Supplementation ◽  
Relevant Research ◽  
Beneficial Effects ◽  
Current Review ◽  
Wide Range ◽  
Research Findings ◽  
Multiple Health

Ever since discovering the fat-soluble secosteroid vitamin D, an abundance of research has been conducted on the molecular mechanisms for the multiple health benefits of this nutrient. Studies on the beneficial effects of vitamin D supplementation have found appreciable evidence suggesting that it may play a more prime role than initially presumed. Though it has largely been implicated in bone pathophysiology, novel research on vitamin D indicates its fundamental involvement in a wide range of disease processes through its multiple systemic effects, including but not limited to metabolic, cardiovascular, anti-inflammatory, antineoplastic, antioxidant, neuroprotective, and immune actions. Recent work has yielded important mechanistic insights into the functions of vitamin D in mediating immunity. The present work sheds light on the metabolism and immune response mechanisms of vitamin D. Current review is based on a thorough search of the available relevant research findings of the metabolic transformations of vitamin D and the molecular basis of its role in immunity. Apart from its classical mechanistic control of mineral homeostasis, vitamin D has immunomodulatory effects through various mechanisms at both systemic and cellular levels. Disruption of vitamin D reliant molecular pathways in the regulation of immune response can potentially result in the development and/or progression of autoimmune and infective processes.[GMJ.2021;10:e2097]

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