scholarly journals The Role of Streptococcal Cell-Envelope Proteases in Bacterial Evasion of the Innate Immune System

2021 ◽  
pp. 1-20
Author(s):  
Sophie McKenna ◽  
Kristin Krohn Huse ◽  
Sean Giblin ◽  
Max Pearson ◽  
Mohammed Said Majid Al Shibar ◽  
...  
Keyword(s):  
Immune System ◽  
Serine Proteases ◽  
Cell Envelope ◽  
In Vivo Studies ◽  
Host Immune System ◽  
Group B Streptococci ◽  
Signalling Molecules ◽  
Group B

Bacteria possess the ability to evolve varied and ingenious strategies to outwit the host immune system, instigating an evolutionary arms race. Proteases are amongst the many weapons employed by bacteria, which specifically cleave and neutralize key signalling molecules required for a coordinated immune response. In this article, we focus on a family of S8 subtilisin-like serine proteases expressed as cell-envelope proteases (CEPs) by group A and group B streptococci. Two of these proteases known as <i>Streptococcus pyogenes</i> CEP (SpyCEP) and C5a peptidase cleave the chemokine CXCL8 and the complement fragment C5a, respectively. Both CXCL8 and C5a are potent neutrophil-recruiting chemokines, and by neutralizing their activity, streptococci evade a key defence mechanism of innate immunity. We review the mechanisms by which CXCL8 and C5a recruit neutrophils and the characterization of SpyCEP and C5a peptidase, including both in vitro and in vivo studies. Recently described structural insights into the function of this CEP family are also discussed. We conclude by examining the progress of prototypic vaccines incorporating SpyCEP and C5a peptidase in their preparation. Since streptococci-producing SpyCEP and C5a peptidase are responsible for a considerable global disease burden, targeting these proteases by vaccination strategies or by small-molecule antagonists should provide protection from and promote the resolution of streptococcal infections.

scholarly journals Prospects of honey in fighting against COVID-19: pharmacological insights and therapeutic promises

2020 ◽  
Author(s):  
Khandkar Shaharina Hossain ◽  
Md. Golzar Hossain ◽  
Akhi Moni ◽  
Mahbubur Rahman ◽  
Umma Habiba Rahman ◽  
...  
Keyword(s):  
Immune System ◽  
Chronic Diseases ◽  
Fungal Infections ◽  
Antimicrobial Activities ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Host Immune System ◽  
Varicella Zoster

Honey and its various ingredients have been in limelight as an effective natural therapy capable of normalizing the situation by attenuating acute inflammation through encouraging immune response. Several studies have proved its potential healing capability against numerous chronic diseases/conditions, including pulmonary disorders, cardiac disorders, diabetes, hypertension, autophagy dysfunction, bacterial and fungal infections. More importantly, honey showed its virucidal effect on several enveloped viruses such as HIV, influenza virus, herpes simplex, and varicella zoster virus. Honey may be beneficial for patients with COVID-19 caused by an enveloped virus SARS-CoV-2 through simultaneously boosting the host immune system, improving comorbid conditions and antiviral activities. Moreover, a clinical trial of honey on COVID-19 patients has been undergoing. In this review, we summarized the potential benefits of honey and its ingredients in the context of antimicrobial activities, numerous chronic diseases, and host immune system and thereby tried to establish a relationship with honey for the treatment of COVID-19. This review will be helpful to reconsider the insights into the possible potential therapeutic effects of honey in the context of COVID-19 pandemic. However, the effects of honey on SARS-CoV-2 replication and/or host immune system need to be further investigated by in vitro and in vivo studies.

scholarly journals Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Poushali Chakraborty ◽  
Sapna Bajeli ◽  
Deepak Kaushal ◽  
Bishan Dass Radotra ◽  
Ashwani Kumar
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune System ◽  
Biofilm Formation ◽  
Antimycobacterial Activity ◽  
Drug Tolerance ◽  
Host Immune System ◽  
Tissue Sections ◽  
Slow Growing

AbstractTuberculosis is a chronic disease that displays several features commonly associated with biofilm-associated infections: immune system evasion, antibiotic treatment failures, and recurrence of infection. However, although Mycobacterium tuberculosis (Mtb) can form cellulose-containing biofilms in vitro, it remains unclear whether biofilms are formed during infection in vivo. Here, we demonstrate the formation of Mtb biofilms in animal models of infection and in patients, and that biofilm formation can contribute to drug tolerance. First, we show that cellulose is also a structural component of the extracellular matrix of in vitro biofilms of fast and slow-growing nontuberculous mycobacteria. Then, we use cellulose as a biomarker to detect Mtb biofilms in the lungs of experimentally infected mice and non-human primates, as well as in lung tissue sections obtained from patients with tuberculosis. Mtb strains defective in biofilm formation are attenuated for survival in mice, suggesting that biofilms protect bacilli from the host immune system. Furthermore, the administration of nebulized cellulase enhances the antimycobacterial activity of isoniazid and rifampicin in infected mice, supporting a role for biofilms in phenotypic drug tolerance. Our findings thus indicate that Mtb biofilms are relevant to human tuberculosis.

scholarly journals Demonstration of opsonic activity and in vivo protection against group B streptococci type III by Streptococcus pneumoniae type 14 antisera.

1978 ◽  
Vol 148 (3) ◽  
pp. 776-786 ◽  
Author(s):  
G W Fischer ◽  
G H Lowell ◽  
M H Crumrine ◽  
J W Bass
Keyword(s):  
Streptococcus Pneumoniae ◽  
Rat Model ◽  
In Vivo Studies ◽  
Group B Streptococci ◽  
Opsonic Activity ◽  
Type Iii ◽  
Neonatal Group ◽  
Group B ◽  
Type 3

The present studies demonstrate that antisera directed against Streptococcus pneumoniae type 14 is opsonic for group B streptococci type III in a neutrophile-mediated bactericidal assay. Specificity was demonstrated by the observations that group B streptococci type III and S. pneumoniae type 14 adsorbed the opsonic activity of anti-S. pneumoniae type 14 antisera. Group B streptococci strain 090R (devoid of type antigens) and S. pneumoniae type 3, did not remove the opsonic activity of anti-S. pneumoniae type 14 serum. In vivo studies using a suckling rat model of neonatal group B streptococcal type III sepsis demonstrated that antisera directed against S. pneumoniae type 14 was highly protective.

scholarly journals Antitumor and immunomodulatory activity of Inonotus obliquus

2017 ◽  
Vol 63 (2) ◽  
pp. 48-58 ◽  
Author(s):  
Justyna Staniszewska ◽  
Marcin Szymański ◽  
Ewa Ignatowicz
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Good Alternative ◽  
Immunomodulatory Activity ◽  
Host Immune System ◽  
Protein Synthesis Inhibition ◽  
Inonotus Obliquus ◽  
Different Types

SummaryThe article presents the antitumor and immunomodulatory activity of compounds and extracts fromInonotus obliquus.Polysaccharides isolated from sclerotium have a direct antitumor effect due to protein synthesis inhibition in tumor cells. Polysaccharides derived from the mycelium function by activating the immune system. Due to the limited toxicity of these substances, both extracts as well as isolated and purified chemicals may be a good alternative to current chemotherapy and play a role in cancer prevention.In vitroexperiments have shown the inhibition of inflammation with the influence of action ofI. obliquusextracts; however,in vivoexperiments on animals implanted with tumor cells of different types have shown the activation of the host immune system. This led to decrease in tumor mass and prolonged survival. The immunomodulatory mechanism of action is complex and it seems that stimulation of macrophages and induction of apoptosis in cancer cells is of great importance.

scholarly journals Rescuing the Host Immune System by Targeting the Immune Evasion Complex ORF8-IRF3 in SARS-CoV-2 Infection with Natural Products Using Molecular Modeling Approaches

2021 ◽  
Vol 19 (1) ◽  
pp. 112
Author(s):  
Aqel Albutti
Keyword(s):  
Immune System ◽  
Immune Evasion ◽  
Simulation Analysis ◽  
Dynamic Properties ◽  
Natural Compounds ◽  
Host Immune System ◽  
Structural Dynamic ◽  
Novel Drugs

The perennial emergence of SARS-CoV-2 and its new variants causing upper respiratory complexities since December 2019 has aggravated the pandemic situation around the world. SARS-CoV-2 encodes several proteins among which ORF8 is a novel factor that is unique to SARS-CoV-2 only and is reported to help the virus in disease severity and immune evasion. ORF8-IRF3 complex induces endoplasmic reticulum stress, thus helps in the evasion of immune response. Consequently, targeting the ORF8-IRF3 complex is considered as a prime target for the discovery of novel drugs against SARS-CoV-2. In this regard, computational methods are of great interest to fast track the identification and development of novel drugs. Virtual screening of South African Natural Compounds Database (SANCDB), followed by docking and molecular dynamics (MD) simulation analysis, were performed to determine novel natural compounds. Computational molecular search and rescoring of the SANCDB database followed by induced-fit docking (IFD) protocol identified Quercetin 3-O-(6″-galloyl)-beta-D-galactopyranoside (SANC00850), Tribuloside (SANC01050), and Rutin (SANC00867) are the best scoring compounds. Structural-dynamic properties assessment revealed that these three compounds have stable dynamics, compactness, and a higher number of hydrogen bonds. For validation, we used MM/GBSA, in silico bioactivity estimation and dissociation constant (KD) approaches, which revealed that these compounds are the more potent inhibitors of the ORF8-IRF3 complex and would rescue the host immune system potentially. These compounds need further in vitro and in vivo validations to be used as therapeutics against SARS-CoV-2 to rescue the host immune system during COVID-19 infection.

Traditional Medicines, HIV, and Related Infections

2011 ◽  
Vol 23 (1) ◽  
pp. 159-164 ◽  
Author(s):  
M. Patel ◽  
P. Bessong ◽  
H. Liu
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Ethical Issues ◽  
Mechanisms Of Action ◽  
Antiretroviral Drugs ◽  
In Vivo Studies ◽  
Traditional Medicines ◽  
Anti Hiv

Traditional medicines are an integral part of health care worldwide, even though their efficacy has not been scientifically proven. HIV-infected individuals may use them singularly or in combination with conventional medicines. Many in vitro studies have proven the anti-HIV, anti- Candida, and anti–herpes simplex virus potential of traditional plants and identified some of the mechanisms of action. Very few in vivo studies are available that involve a small number of participants and show controversial results. In addition, knowledge is limited of the role of traditional medicines in the enhancement of the immune system. The use of traditional medicines with antiretroviral drugs (ARVs) has created a problem because drug interactions compromise the efficacy of ARVs. Several currently popular plants have been studied in the laboratory for their interaction with ARVs, with disadvantageous results. Unfortunately, no clinical trials are available. The science of traditional medicines is relatively new and is at present being modernized worldwide. However, there are still ethical issues regarding traditional medicines that need to be addressed—for example, regulations regarding quality control and standardization of medicines, regulation and education of healers who deliver these medicines, and unregulated clinical trials. The workshop addressed the following questions about traditional medicine and their use in HIV infection: What are the mechanisms of action of anti-HIV traditional medicines? Should traditional medicines be used in conjunction with ARV? Do traditional medicines enhance the immune system? Should medicinal plants be used for the control of oral infections associated with HIV? What are the ethical issues surrounding the use of traditional medicines for the treatment of HIV and associated infections?

scholarly journals Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 789 ◽  
Author(s):  
Mattia Bellan ◽  
Laura Andreoli ◽  
Chiara Mele ◽  
Pier Paolo Sainaghi ◽  
Cristina Rigamonti ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Autoimmune Diseases ◽  
Convincing Evidence ◽  
In Vivo Studies ◽  
Human Immune System ◽  
Therapeutic Implications ◽  
Wide Range

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

scholarly journals Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18 and SARS-CoV-2-specific IgA

2020 ◽  
Author(s):  
Wanyin Tao ◽  
Shu Zhu ◽  
Guorong Zhang ◽  
Xiaofang Wang ◽  
Meng Guo ◽  
...  
Keyword(s):  
Immune System ◽  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Disease Severity ◽  
Specific Cell ◽  
Host Immune System ◽  
Inflammatory Factor ◽  
Cytokine Storm

The current global COVID-19 pandemic is caused by beta coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which already infected over 10 million and caused 500 thousand deaths by June 2020. Overproduction of cytokines triggered by COVID-19 infection, known as "cytokine storm", is a highly risk factor associated with disease severity. However, how COVID-19 infection induce cytokine storm is still largely unknown. Accumulating in vitro and in vivo evidence suggests that gut is also susceptible to COVID19 infection: Human intestinal organoids, an in vitro model which mimic the specific cell type and spatial structure of the intestine, were susceptible to SARS-CoV2 infection; A significant fraction of patients reported gut symptoms; Viral RNA may persist for more than 30 days and infectious virus could be isolated in fecal samples. The gastrointestinal tract is the primary site of interaction between the host immune system with symbiotic and pathogenic microorganisms. The bacteria resident in our gastrointestinal tract, known as gut microbiota, is important to maintain the homeostasis of our immune system. While imbalance of gut microbiota, or dysbiosis, is associated with multiple inflammation diseases5. It's possible that SARS-CoV-2 infection may lead to alternation of gut microbiota thus worsen the host symptom. IL-18 is a proinflammatory cytokine produced multiple enteric cells, including intestinal epithelial cells (IECs), immune cells as well as enteric nervous system, and was shown to increase in the serum of COVID-19 patients. Immunoglobin A (IgA) is mainly produced in the mucosal surfaces, in humans 40-60mg kg-1 day-1 than all other immunoglobulin isotypes combined, and at least 80% of all plasma cells are located in the intestinal lamina propria. Recent study showed that SARS-CoV-2 specific IgA in the serum is positively correlate with the disease severity in COVID-19 patients11. Here we investigated the alterations of microbiota in COVID-19 patients, and its correlation with inflammatory factor IL-18 and SARS-CoV2 specific IgA.

scholarly journals MTS1338, a smallMycobacterium tuberculosisRNA, regulates transcriptional shifts consistent with bacterial adaptation for entering into dormancy and survival within host macrophages

2018 ◽  
Author(s):  
Elena G. Salina ◽  
Artem Grigorov ◽  
Yulia Skvortsova ◽  
Konstantin Majorov ◽  
Oksana Bychenko ◽  
...  
Keyword(s):  
Immune System ◽  
Ex Vivo ◽  
Host Immune System ◽  
Rna Seq ◽  
Bacterial Adaptation ◽  
Translational Activity ◽  
Non Coding Rna ◽  
Constitutive Overexpression

AbstractSmall non-coding RNAs play a significant role in bacterial adaptation to changing environmental conditions. We investigated the dynamics of expression of MTS1338, a small non-coding RNA ofMycobacterium tuberculosis, in the mouse modelin vivo, regulation of its expression in theex vivoinfected macrophages, and the consequences of its overexpression in bacterial cultures. Here we demonstrate that MTS1338 significantly contributes to host-pathogen interactions. Activation of the host immune system triggered NO-inducible up-regulation of MTS1338 in macrophage-engulfed mycobacteria. Constitutive overexpression of MTS1338 in cultured mycobacteria improved their survivalin vitrounder low pH conditions. MTS1338 up-regulation launched a spectrum of shifts in the transcriptome profile similar to those reported forM. tuberculosisadaptation to hostile intra-macrophage environment. Using the RNA-seq approach, we demonstrate that gene expression changes accompanying MTS1338 overexpression indicate reduction in translational activity and bacterial growth, which is consistent with entering the dormant state. Taken together, our results suggest a direct involvement on this sRNA in the interplay between mycobacteria and the host immune system during infectious process.

scholarly journals Anti-cancer potential of natural products: recent trends, scope and relevance

2020 ◽  
Vol 9 (1) ◽  
pp. 902-907
Keyword(s):  
Natural Products ◽  
Immune System ◽  
Herbal Medicines ◽  
Data Interpretation ◽  
In Vivo Studies ◽  
Bioactive Substances ◽  
Herbal Products ◽  
Culturing Conditions

Disease can occur due to alterations in many physiological processes. A variety of factorsare known to be involved in the progression of cancer, a chronic diseasethat occurs due to permissible proliferative signaling, avoiding growth suppressors, resisting cell death, allowing replicative immortality, induction of angiogenesis, and inducing invasion and metastasis, along with reprogramming of metabolic pathways involved in energy production and avoiding the host immune response for cell destruction. Treatment of such a multifactorial disease has very less cure rate because of the singular agents tried in the past for targeting. Molecular level studies with deeper insight are urgently neededthat focus on the most promising herbal-derived bioactive substances for which thorough research was carried out in the literature in various data-bases such as PUB-MED, MEDLINE, SCOPUS indexed journals etc. to look for systematic reviews of the protocols or data interpretation, natural drug/immunological properties and validation. As immune system plays avery important role in the proliferation or suppression of cancer and other autoimmune diseases, It is the dire need to study the effect of such natural compound on the immune system so that a possible drug target or epitope can be identified for the treatment of such diseases. In nutshell there are many nonclinical in vitro and in vivo studies on herbal medicines which commonly supports the traditional therapeutic claims. It has been seen from the previos studies in literature that the yield and composition of bioactive compounds derived from plants are dependent upon the production source,culturing conditions and extraction protocols.Therefore appropriate optimization conditions would certainly assist the medical and scientific fraternity to accept herbal products as potential candidates for cancer treatment. In this article we explored the different natural products, their immunological effects concerning cancer with no or negligible side effects. However,one has to look for potential herb–drug or herb-epitope interactions and how immune system responds to such drugs.

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