scholarly journals Host Immune Responses to Clostridioides difficile: Toxins and Beyond

2021 ◽  
Vol 12 ◽  
Author(s):  
Britt Nibbering ◽  
Dale N. Gerding ◽  
Ed J. Kuijper ◽  
Romy D. Zwittink ◽  
Wiep Klaas Smits
Keyword(s):  
Immune Responses ◽  
Bacterial Infections ◽  
Plasma Cells ◽  
Current Knowledge ◽  
Treatment Options ◽  
T Cell Response ◽  
Medical Community ◽  
Future Research ◽  
Host Immune Responses ◽  
Clostridioides Difficile

Clostridioides difficile is often resistant to the actions of antibiotics to treat other bacterial infections and the resulting C. difficile infection (CDI) is among the leading causes of nosocomial infectious diarrhea worldwide. The primary virulence mechanism contributing to CDI is the production of toxins. Treatment failures and recurrence of CDI have urged the medical community to search for novel treatment options. Strains that do not produce toxins, so called non-toxigenic C. difficile, have been known to colonize the colon and protect the host against CDI. In this review, a comprehensive description and comparison of the immune responses to toxigenic C. difficile and non-toxigenic adherence, and colonization factors, here called non-toxin proteins, is provided. This revealed a number of similarities between the host immune responses to toxigenic C. difficile and non-toxin proteins, such as the influx of granulocytes and the type of T-cell response. Differences may reflect genuine variation between the responses to toxigenic or non-toxigenic C. difficile or gaps in the current knowledge with respect to the immune response toward non-toxigenic C. difficile. Toxin-based and non-toxin-based immunization studies have been evaluated to further explore the role of B cells and reveal that plasma cells are important in protection against CDI. Since the success of toxin-based interventions in humans to date is limited, it is vital that future research will focus on the immune responses to non-toxin proteins and in particular non-toxigenic strains.

scholarly journals The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

2022 ◽  
Vol 23 (1) ◽  
pp. 525
Author(s):  
Tarina Sharma ◽  
Anwar Alam ◽  
Aquib Ehtram ◽  
Anshu Rani ◽  
Sonam Grover ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Current Knowledge ◽  
Immune Effector ◽  
Host Immune Responses ◽  
Intrinsically Disordered ◽  
Multiple Strategies ◽  
Latent Stage ◽  
Immune Mediated ◽  
Critical Edge

Mycobacterium tuberculosis (M.tb) is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. M.tb escapes from host macrophage through evasion or subversion of immune effector functions. M.tb genome codes for PE/PPE/PE_PGRS proteins, which are intrinsically disordered, redundant and antigenic in nature. These proteins perform multiple functions that intensify the virulence competence of M.tb majorly by modulating immune responses, thereby affecting immune mediated clearance of the pathogen. The highly repetitive, redundant and antigenic nature of PE/PPE/PE_PGRS proteins provide a critical edge over other M.tb proteins in terms of imparting a higher level of virulence and also as a decoy molecule that masks the effect of effector molecules, thereby modulating immuno-surveillance. An understanding of how these proteins subvert the host immunological machinery may add to the current knowledge about M.tb virulence and pathogenesis. This can help in redirecting our strategies for tackling M.tb infections.

scholarly journals Treatment options in type-2 low asthma

2020 ◽  
pp. 2000528 ◽  
Author(s):  
Timothy SC Hinks ◽  
Stewart J Levine ◽  
Guy G Brusselle
Keyword(s):  
Severe Asthma ◽  
Bacterial Infections ◽  
Current Knowledge ◽  
Treatment Options ◽  
Occupational Exposures ◽  
Evidence Base ◽  
Type I ◽  
Eosinophilic Asthma ◽  
Ongoing Research

Monoclonal antibodies targeting IgE or the type-2 cytokines IL-4, IL-5 and IL-13 are proving highly effective in reducing exacerbations and symptoms in people with severe allergic and eosinophilic asthma respectively. However, these therapies are not appropriate for 30–50% of patients in severe asthma clinics who present with non-allergic, non-eosinophilic, “type-2 low” asthma. These patients constitute an important and common clinical asthma phenotype, driven by distinct, though poorly understood pathobiological mechanisms. In this review we describe the heterogeneity and clinical characteristics of type-2 low asthma and summarise current knowledge on the underlying pathobiological mechanisms, which includes neutrophilic airway inflammation often associated with smoking, obesity, occupational exposures and may be driven by persistent bacterial infections and by activation of a recently-described IL-6 pathway. We review the evidence base underlying existing treatment options for specific treatable traits which can be identified and addressed. We particularly focus on severe asthma as opposed to difficult-to-treat asthma, on emerging data on the identification of airway bacterial infection, on the increasing evidence base for the use of long-term low-dose macrolides, a critical appraisal of bronchial thermoplasty, and evidence for the use of biologics in type-2 low disease. Finally we review ongoing research into other pathways including TNF, IL-17, resolvins, apolipoproteins, type I interferons, IL-6 and mast cells. We suggest that type-2 low disease frequently presents opportunities for identification and treatment of tractable clinical problems and is currently a rapidly evolving field with potential for the development of novel targeted therapeutics.

scholarly journals Citrobacter amalonaticus Inhibits the Growth of Citrobacter rodentium in the Gut Lumen

mBio ◽  
2021 ◽  
Author(s):  
Caroline Mullineaux-Sanders ◽  
Danielle Carson ◽  
Eve G. D. Hopkins ◽  
Izabela Glegola-Madejska ◽  
Alejandra Escobar-Zepeda ◽  
...  
Keyword(s):  
Immune Responses ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Citrobacter Rodentium ◽  
Colonization Resistance ◽  
Host Immune Responses ◽  
Citrobacter Amalonaticus

Gut bacterial infections involve three-way interactions between virulence factors, the host immune responses, and the microbiome. While the microbiome erects colonization resistance barriers, pathogens employ virulence factors to overcome them.

scholarly journals Drawing Comparisons between SARS-CoV-2 and the Animal Coronaviruses

2020 ◽  
Vol 8 (11) ◽  
pp. 1840
Author(s):  
Souvik Ghosh ◽  
Yashpal S. Malik
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Effective Control ◽  
Tissue Tropism ◽  
Prevention Strategies ◽  
Host Immune Responses ◽  
Clinical Presentations ◽  
Control And Prevention ◽  
Diversity Transmission ◽  
Complex Origin

The COVID-19 pandemic, caused by a novel zoonotic coronavirus (CoV), SARS-CoV-2, has infected 46,182 million people, resulting in 1,197,026 deaths (as of 1 November 2020), with devastating and far-reaching impacts on economies and societies worldwide. The complex origin, extended human-to-human transmission, pathogenesis, host immune responses, and various clinical presentations of SARS-CoV-2 have presented serious challenges in understanding and combating the pandemic situation. Human CoVs gained attention only after the SARS-CoV outbreak of 2002–2003. On the other hand, animal CoVs have been studied extensively for many decades, providing a plethora of important information on their genetic diversity, transmission, tissue tropism and pathology, host immunity, and therapeutic and prophylactic strategies, some of which have striking resemblance to those seen with SARS-CoV-2. Moreover, the evolution of human CoVs, including SARS-CoV-2, is intermingled with those of animal CoVs. In this comprehensive review, attempts have been made to compare the current knowledge on evolution, transmission, pathogenesis, immunopathology, therapeutics, and prophylaxis of SARS-CoV-2 with those of various animal CoVs. Information on animal CoVs might enhance our understanding of SARS-CoV-2, and accordingly, benefit the development of effective control and prevention strategies against COVID-19.

scholarly journals New Host-Directed Therapeutics for the Treatment of Clostridioides difficile Infection

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Jourdan A. Andersson ◽  
Alex G. Peniche ◽  
Cristi L. Galindo ◽  
Prapaporn Boonma ◽  
Jian Sha ◽  
...  
Keyword(s):  
Immune Responses ◽  
Murine Model ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Drug Efficacy ◽  
Innate Immune ◽  
Rna Seq ◽  
Human Pathogens ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACT Frequent and excessive use of antibiotics primes patients to Clostridioides difficile infection (CDI), which leads to fatal pseudomembranous colitis, with limited treatment options. In earlier reports, we used a drug repurposing strategy and identified amoxapine (an antidepressant), doxapram (a breathing stimulant), and trifluoperazine (an antipsychotic), which provided significant protection to mice against lethal infections with several pathogens, including C. difficile. However, the mechanisms of action of these drugs were not known. Here, we provide evidence that all three drugs offered protection against experimental CDI by reducing bacterial burden and toxin levels, although the drugs were neither bacteriostatic nor bactericidal in nature and had minimal impact on the composition of the microbiota. Drug-mediated protection was dependent on the presence of the microbiota, implicating its role in evoking host defenses that promoted protective immunity. By utilizing transcriptome sequencing (RNA-seq), we identified that each drug increased expression of several innate immune response-related genes, including those involved in the recruitment of neutrophils, the production of interleukin 33 (IL-33), and the IL-22 signaling pathway. The RNA-seq data on selected genes were confirmed by quantitative real-time PCR (qRT-PCR) and protein assays. Focusing on amoxapine, which had the best anti-CDI outcome, we demonstrated that neutralization of IL-33 or depletion of neutrophils resulted in loss of drug efficacy. Overall, our lead drugs promote disease alleviation and survival in the murine model through activation of IL-33 and by clearing the pathogen through host defense mechanisms that critically include an early influx of neutrophils. IMPORTANCE Clostridioides difficile is a spore-forming anaerobic bacterium and the leading cause of antibiotic-associated colitis. With few therapeutic options and high rates of disease recurrence, the need to develop new treatment options is urgent. Prior studies utilizing a repurposing approach identified three nonantibiotic Food and Drug Administration-approved drugs, amoxapine, doxapram, and trifluoperazine, with efficacy against a broad range of human pathogens; however, the protective mechanisms remained unknown. Here, we identified mechanisms leading to drug efficacy in a murine model of lethal C. difficile infection (CDI), advancing our understanding of the role of these drugs in infectious disease pathogenesis that center on host immune responses to C. difficile. Overall, these studies highlight the crucial involvement of innate immune responses, as well as the importance of immunomodulation as a potential therapeutic option to combat CDI.

scholarly journals The genome sequence of the avian vampire fly (Philornis downsi), an invasive nest parasite of Darwins finches in Galpagos

2021 ◽  
Author(s):  
Melia Romine ◽  
Sarah A Knutie ◽  
Carly M Crow ◽  
Grace J Vaziri ◽  
Jaime Chaves ◽  
...  
Keyword(s):  
Immune Responses ◽  
Insecticide Resistance ◽  
Genome Assembly ◽  
Gene Families ◽  
Mitigation Strategies ◽  
Future Research ◽  
Host Immune Responses ◽  
Philornis Downsi ◽  
Genomic Resource ◽  
Mitigation Methods

The invasive avian vampire fly (Philornis downsi) is considered one of the greatest threats to the unique and endemic avifauna of the Galpagos Islands, Ecuador. The fly parasitizes nearly every passerine species, including Darwins finches, in the Galpagos. The fly is thought to have been introduced from mainland Ecuador, although the full pathway of invasion is not yet known. The majority of research to date has focused on the effects of the fly on the fitness of avian hosts and explorations of mitigation methods. A lag in research related to the genetics of this invasion demonstrates, in part, a need to develop full-scale genomic resources with which to address further questions within this system. In this study, an adult P. downsi collected from San Cristobal Island within the Galpagos archipelago was sequenced to generate a high-quality genome assembly. We examined various features of the genome (e.g., coding regions, non-coding transposable elements) and carried out comparative genomics analysis against other dipteran genomes. We identified lists of gene families that are significantly expanding/contracting in P. downsi >that are related to insecticide resistance, detoxification, and potential feeding ecology and counter defense against host immune responses. The P. downsi genome assembly provides an important foundational resource for studying the molecular basis of its successful invasion in the Galpagos and the dynamics of its population across multiple islands. The findings of significantly changing gene families associated with insecticide resistance and immune responses highlight the need for further investigations into the role of different gene families in aiding the flys successful invasion. Furthermore, this genomic resource will also better help inform future research studies and mitigation strategies aimed at minimizing the flys impact on the birds of the Galpagos.

scholarly journals Immunological Responses and Survival Outcome in HIV and SARS-CoV-2 Coinfected Patients

2021 ◽  
Vol SP (2) ◽  
Author(s):  
Uzma A. Jilani ◽  
Zulhabri Othman ◽  
Syed A. Jilani
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
People Living With Hiv ◽  
Immunological Responses ◽  
Host Immune Responses ◽  
Acute Infections ◽  
Living With Hiv ◽  
The Impact ◽  
Special Subgroup ◽  
Hiv Aids

The coronavirus disease 2019 (COVID‐19) has created a worldwide crisis, raising fears and concerns regarding clinical outcomes in patients with comorbidities. Some of the highly prevalent communicable and non-communicable diseases worldwide are cardiovascular diseases, diabetes, HIV/AIDS, and hepatitis B and C, which reduce the host immune responses to concurrent acute infections. Despite over 170 million confirmed cases of COVID‐19 worldwide as of 24 June 2021, insufficient data is reporting the prognosis of HIV and SARS-CoV-2 co‐infection. This narrative review aims to present current knowledge on the impact of SARS-CoV-2 on people living with HIV/AIDS, in terms of immunological responses and clinical outcome. Although some studies have been performed and are in progress to determine the impact of SARS-CoV-2 infection on patients living with HIV/AIDS, controversies still exist whether COVID-19 severity and mortality are higher among this special subgroup or similar to the general population.

scholarly journals Coronavirus Disease 2019 (COVID-19): Pathogenesis, Immune Responses, and Treatment Options

2020 ◽  
Author(s):  
Nandini Eswaran ◽  
Shwetha Krishna
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Defense Mechanisms ◽  
Current Knowledge ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Evolutionary Process ◽  
Effective Vaccine ◽  
Novel Coronavirus

Background: The emergence and the spread of the novel coronavirus or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating impact on the economy and has become a pressing issue globally. Due to the significant increase in the number of confirmed cases and death tolls worldwide, and certain countries reporting second waves, there is an immediate need for an effective vaccine or other therapeutic intervention to control the spread of the disease. Improving our understanding on the host’s anti-viral immune response on SARS-CoV-2 infection, the potential immune evasion mechanisms adopted by the virus, and the speculated role of antibody dependent enhancement (ADE) in coronavirus disease 2019 (COVID-19) pathogenesis will aid in identifying and designing effective therapeutics. Aim: This review aims to provide an in-depth view of the current knowledge available on the range of host defense mechanisms activated by SARS-CoV-2 infection and various immune evasion mechanisms utilized by the virus. In addition, it also highlights the postulated role of ADE in viral pathogenesis and covers the different preventive and therapeutic options available for the treatment of COVID-19 based on current literature. Discussion: The ongoing COVID-19 pandemic serves as a timely reminder on the constant evolutionary process the virus undergoes to emerge as a novel strain and to spread undetected within the population. Similar to other infectious diseases, the host defence mechanism is triggered, and it plays a central role in dampening viral replication by recruiting immune cells and activating anti-viral mechanisms to control the spread of infection by SARS-CoV-2. However, the virus has adopted different immune evasion mechanisms to circumvent host surveillance to successfully establish infection. Hence, understanding the host’s immune responses triggered by SARS-CoV-2 infection is critical for identifying and designing novel and effective therapeutics. Currently, over 70% of the population are either asymptomatic or they showcase mild to moderate symptoms and reasons for why some people can mount immune responses more quickly than others are unknown. However, a growing body of research speculates that the ADE mechanism may facilitate the SARS-CoV-2 entry and can contribute to severe clinical manifestations. With the constant rise in the number of confirmed cases, there is an immediate need for an effective vaccine to mitigate the spread of the virus. Presently, there is no treatment for COVID-19 although several vaccine candidates are in clinical trials. Therefore, preventive measures like social distancing, isolation, and travel restrictions, may be the key to controlling the rapid spread of COVID-19.

scholarly journals “World in motion” – emulsion adjuvants rising to meet the pandemic challenges

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Derek T. O’Hagan ◽  
Robbert van der Most ◽  
Rushit N. Lodaya ◽  
Margherita Coccia ◽  
Giuseppe Lofano
Keyword(s):  
Immune Responses ◽  
Plasma Cells ◽  
Influenza Pandemic ◽  
H1n1 Influenza ◽  
T Cell Response ◽  
Influenza Vaccines ◽  
Vaccine Adjuvants ◽  
Immunological Responses ◽  
2009 H1n1 ◽  
Human Immunity

AbstractEmulsion adjuvants such as MF59 and AS03 have been used for more than two decades as key components of licensed vaccines, with over 100 million doses administered to diverse populations in more than 30 countries. Substantial clinical experience of effectiveness and a well-established safety profile, along with the ease of manufacturing have established emulsion adjuvants as one of the leading platforms for the development of pandemic vaccines. Emulsion adjuvants allow for antigen dose sparing, more rapid immune responses, and enhanced quality and quantity of adaptive immune responses. The mechanisms of enhancement of immune responses are well defined and typically characterized by the creation of an “immunocompetent environment” at the site of injection, followed by the induction of strong and long-lasting germinal center responses in the draining lymph nodes. As a result, emulsion adjuvants induce distinct immunological responses, with a mixed Th1/Th2 T cell response, long-lived plasma cells, an expanded repertoire of memory B cells, and high titers of cross-neutralizing polyfunctional antibodies against viral variants. Because of these various properties, emulsion adjuvants were included in pandemic influenza vaccines deployed during the 2009 H1N1 influenza pandemic, are still included in seasonal influenza vaccines, and are currently at the forefront of the development of vaccines against emerging SARS-CoV-2 pandemic variants. Here, we comprehensively review emulsion adjuvants, discuss their mechanism of action, and highlight their profile as a benchmark for the development of additional vaccine adjuvants and as a valuable tool to allow further investigations of the general principles of human immunity.

scholarly journals SeXX and COVID-19: Tussle between the Two

2020 ◽  
Author(s):  
Ashlesh Patil ◽  
Jaya Prasad Tripathy ◽  
Vishwajit Deshmukh ◽  
Bharat Sontakke ◽  
Satyendra C. Tripathi
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Occupational Exposures ◽  
Point Of View ◽  
Host Immune Responses ◽  
Social Inequities ◽  
Biological Explanation ◽  
Novel Coronavirus ◽  
Biological Differences

Novel coronavirus disease (COVID-19) has affected nearly 7 million individuals and claimed more than 0.4 million lives to date. There are several reports of gender differences related to infection and death due to COVID-19. This raises important questions such as “Whether there are differences based on gender in risk and severity of infection or mortality rate?” and “What are the biological explanation and mechanisms underlying these differences?” Emerging evidence has proposed sex-based immunological, genetic, and hormonal differences to explain this ambiguity. Besides biological differences, women have also faced social inequities and economic hardships due to this pandemic. Several recent studies have shown that independent of age males are at higher risk for severity and mortality in COVID-19 patients. Although susceptibility to SARS-CoV-2 was found to be similar across both genders in several disease cohorts, a disproportionate death ratio in men can be partly explained by the higher burden of pre-existing diseases and occupational exposures among men. From an immunological point of view, females can engage a more active immune response, which may protect them and counter infectious diseases as compared to men. This attribute of better immune responses towards pathogens is thought to be due to high estrogen levels in females. Here we review the current knowledge about sex differences in susceptibility, the severity of infection and mortality, host immune responses, and the role of sex hormones in COVID-19 disease.

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