Acquired immune heterogeneity and its sources in human helminth infection

SUMMARYSimilarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recentin vitroand immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The ‘trade-off’ between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigensin utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.

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Oxidative Stress Compromises Lymphocyte Function in Neonatal Dairy Calves

Antioxidants ◽

10.3390/antiox10020255 ◽

2021 ◽

Vol 10 (2) ◽

pp. 255

Author(s):

Wilmer Cuervo ◽

Lorraine M. Sordillo ◽

Angel Abuelo

Keyword(s):

Oxidative Stress ◽

Immune Responses ◽

Immune Cell ◽

Lymphocyte Activation ◽

Dairy Calves ◽

Lymphocyte Function ◽

Newborn Calves ◽

Ifn Γ ◽

The Impact

Dairy calves are unable to mount an effective immune response during their first weeks of life, which contributes to increased disease susceptibility during this period. Oxidative stress (OS) diminishes the immune cell capabilities of humans and adult cows, and dairy calves also experience OS during their first month of life. However, the impact that OS may have on neonatal calf immunity remains unexplored. Thus, we aimed to evaluate the impact of OS on newborn calf lymphocyte functions. For this, we conducted two experiments. First, we assessed the association of OS status throughout the first month of age and the circulating concentrations of the cytokines interferon-gamma (IFN-γ) and interleukin (IL) 4, as well as the expression of cytokine-encoding genes IFNG, IL2, IL4, and IL10 in peripheral mononuclear blood cells (PBMCs) of 12 calves. Subsequently, we isolated PBMCs from another 6 neonatal calves to investigate in vitro the effect of OS on immune responses in terms of activation of lymphocytes, cytokine expression, and antibody production following stimulation with phorbol 12-myristate 13-acetate or bovine herpesvirus-1. The results were compared statistically through mixed models. Calves exposed to high OS status in their first month of age showed higher concentrations of IL-4 and expression of IL4 and IL10 and lower concentrations of IFN-γ and expression of IFNG and IL2 than calves exposed to lower OS. In vitro, OS reduced lymphocyte activation, production of antibodies, and protein and gene expression of key cytokines. Collectively, our results demonstrate that OS can compromise some immune responses of newborn calves. Hence, further studies are needed to explore the mechanisms of how OS affects the different lymphocyte subsets and the potential of ameliorating OS in newborn calves as a strategy to augment the functional capacity of calf immune cells, as well as enhance calves’ resistance to infections.

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MICA*019 Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese

Journal of Personalized Medicine ◽

10.3390/jpm11060564 ◽

2021 ◽

Vol 11 (6) ◽

pp. 564

Author(s):

Chin-Man Wang ◽

Keng-Poo Tan ◽

Yeong-Jian Jan Wu ◽

Jing-Chi Lin ◽

Jian-Wen Zheng ◽

...

Keyword(s):

Immune Responses ◽

Significant Risk ◽

Significant Risk Factor ◽

Healthy Controls ◽

Hla B27 ◽

Host Immune Responses ◽

Histocompatibility Complex ◽

High Level ◽

Coding Snp

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.

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Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽

10.3390/vaccines9060629 ◽

2021 ◽

Vol 9 (6) ◽

pp. 629

Author(s):

Megan M. Dunagan ◽

Kala Hardy ◽

Toru Takimoto

Keyword(s):

Immune Response ◽

Immune Responses ◽

Influenza A Virus ◽

Influenza A ◽

Human Populations ◽

Lymphocyte Migration ◽

Host Immune Responses ◽

Mhc Molecules ◽

The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

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Trust, efficacy and ethicacy when testing prisoners for COVID-19

International Journal of Prisoner Health ◽

10.1108/ijph-10-2020-0084 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Steve Lambert ◽

Dean Wilkinson

Keyword(s):

Large Scale ◽

Current System ◽

Epidemiological Studies ◽

Careful Consideration ◽

Power Relationships ◽

England And Wales ◽

Content Type ◽

Large Scale Testing ◽

The Uk ◽

The Impact

Purpose The outbreak of the severe acute respiratory syndrome coronavirus 2 virus and subsequent COVID-19 illness has had a major impact on all levels of society internationally. The extent of the impact of COVID-19 on prison staff and prisoners in England and Wales is unknown. Testing for COVID-19 both asymptomatic and symptomatic, as well as for antibodies, to date, has been minimal. The purpose of this paper is to explore the widespread testing of COVID-19 in prisons poses philosophical and ethical questions around trust, efficacy and ethicacy. Design/methodology/approach This paper is both descriptive, providing an overview of the widespread testing of COVID-19 in prisoners in England and Wales, and conceptual in that it discusses and argues the issues associated with large-scale testing. This paper provides a discussion, using comparative studies, of the issues associated with large-scale testing of prisoners across the prison estate in England and Wales (120 prisons). The issues identified in this paper are contextualised through the lens of COVID-19, but they are equally transferrable to epidemiological studies of any pandemic. Given the prevalence of COVID-19 globally and the lack of information about its spread in prisons, at the time of writing this paper, there is a programme of asymptomatic testing of prisoners. However, there remains a paucity of data on the spread of COVID-19 in prisons because of the progress with the ongoing testing programme. Findings The authors argue that the widespread testing of prisoners requires careful consideration of the details regarding who is included in testing, how consent is gained and how tests are administered. This paper outlines and argues the importance of considering the complex nuance of power relationships within the prison system, among prisoner officers, medical staff and prisoners and the detrimental consequences. Practical implications The widespread testing of COVID-19 presents ethical and practical challenges. Careful planning is required when considering the ethics of who should be included in COVID-19 testing, how consent will be gained, who and how tests will be administered and very practical challenges around the recording and assigning of COVID-19 test kits inside the prison. The current system for the general population requires scanning of barcodes and registration using a mobile number; these facilities are not permitted inside a prison. Originality/value This paper looks at the issues associated with mass testing of prisoners for COVID-19. According to the authors’ knowledge, there has not been any research that looks at the issues of testing either in the UK or internationally. The literature available details countries’ responses to the pandemic rather and scientific papers on the development of vaccines. Therefore, this paper is an original review of some of the practicalities that need to be addressed to ensure that testing can be as successful as possible.

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Construction and characterization of recombinant vaccinia viruses co-expressing a respiratory syncytial virus protein and a cytokine

Journal of General Virology ◽

10.1099/0022-1317-82-9-2107 ◽

2001 ◽

Vol 82 (9) ◽

pp. 2107-2116 ◽

Cited By ~ 20

Author(s):

Teresa R. Johnson ◽

Julie E. Fischer ◽

Barney S. Graham

Keyword(s):

Respiratory Syncytial Virus ◽

Immune Responses ◽

Vaccinia Virus ◽

Antigen Expression ◽

Virus Protein ◽

Recombinant Vaccinia ◽

Vaccinia Viruses ◽

Ifn Γ ◽

Syncytial Virus ◽

The Impact

Recombinant vaccinia viruses are well-characterized tools that can be used to define novel approaches to vaccine formulation and delivery. While vector co-expression of immune mediators has enormous potential for optimizing the composition of vaccine-induced immune responses, the impact on antigen expression and vector antigenicity must also be considered. Co-expression of IL-4 increased vaccinia virus vector titres, while IFN-γ co-expression reduced vaccinia virus replication in BALB/c mice and in C57BL/6 mice infected with some recombinant viruses. Protection against respiratory syncytial virus (RSV) challenge was similar in mice immunized with vaccinia virus expressing RSV G glycoprotein and IFN-γ, even though the replication efficiency of the vector was diminished. These data demonstrate the ability of vector-expressed cytokine to influence the virulence of the vector and to direct the development of selected immune responses. This suggests that the co-expression of cytokines and other immunomodulators has the potential to improve the safety of vaccine vectors while improving the immunogenicity of vaccine antigens.

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Microfluidic deep mutational scanning of the human executioner caspases reveals differences in structure and regulation

Cell Death Discovery ◽

10.1038/s41420-021-00799-0 ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Hridindu Roychowdury ◽

Philip A. Romero

Keyword(s):

Large Scale ◽

Cysteine Proteases ◽

Amino Acid Substitutions ◽

Substrate Preferences ◽

Functional Differences ◽

Caspase Family ◽

Executioner Caspases ◽

The Impact ◽

Human Caspase

AbstractThe human caspase family comprises 12 cysteine proteases that are centrally involved in cell death and inflammation responses. The members of this family have conserved sequences and structures, highly similar enzymatic activities and substrate preferences, and overlapping physiological roles. In this paper, we present a deep mutational scan of the executioner caspases CASP3 and CASP7 to dissect differences in their structure, function, and regulation. Our approach leverages high-throughput microfluidic screening to analyze hundreds of thousands of caspase variants in tightly controlled in vitro reactions. The resulting data provides a large-scale and unbiased view of the impact of amino acid substitutions on the proteolytic activity of CASP3 and CASP7. We use this data to pinpoint key functional differences between CASP3 and CASP7, including a secondary internal cleavage site, CASP7 Q196 that is not present in CASP3. Our results will open avenues for inquiry in caspase function and regulation that could potentially inform the development of future caspase-specific therapeutics.

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PFAS Environmental Pollution and Antioxidant Responses: An Overview of the Impact on Human Field

10.20944/preprints202010.0086.v1 ◽

2020 ◽

Author(s):

Marco Bonato ◽

Francesca Corrà ◽

Marta Bellio ◽

Laura Guidolin ◽

Laura Tallandini ◽

...

Keyword(s):

Environmental Pollution ◽

Human Health ◽

Antioxidant Defense System ◽

Epidemiological Studies ◽

Negative Effects ◽

Environmental Distribution ◽

Commercial Applications ◽

The Impact

Due to their unique properties, perfluorinated substances (PFAS) are widely used in multiple industrial and commercial applications, but they are toxic for animals, humans included. This review presents some available data on the PFAS environmental distribution in the world, and in particular in Europe and in Veneto region of Italy, where it has become a serious problem for human health. The consumption of contaminated food and drinking water is considered one of the major source of exposure for humans. Worldwide epidemiological studies report the negative effects that PFAS have on human health, due to environmental pollution, including infertility, steroid hormone perturbation, thyroid, liver and kidney disorders and metabolic disfunctions. In vitro and in vivo researches correlated PFAS exposure to oxidative stress effects (in mammals as well as in other vertebrates of human interest), produced by a PFAS-induced increase of reactive oxygen species formation. The cellular antioxidant defense system is activated by PFAS, but it is only partially able to avoid the oxidative damage to biomolecules.

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Immunostimulatory Effects of Recombinant Erysipelothrix rhusiopathiae Expressing Porcine Interleukin-18 in Mice and Pigs

Clinical and Vaccine Immunology ◽

10.1128/cvi.00342-12 ◽

2012 ◽

Vol 19 (9) ◽

pp. 1393-1398 ◽

Cited By ~ 2

Author(s):

Yohsuke Ogawa ◽

Yu Minagawa ◽

Fang Shi ◽

Masahiro Eguchi ◽

Yoshihiro Muneta ◽

...

Keyword(s):

Immune Responses ◽

Peritoneal Macrophages ◽

Erysipelothrix Rhusiopathiae ◽

Interleukin 18 ◽

Murine Splenocytes ◽

Content Type ◽

Immunostimulatory Effect ◽

Ifn Γ ◽

Acquired Immune Responses

ABSTRACTInterleukin-18 (IL-18), which was originally called gamma interferon (IFN-γ)-inducing factor, has been shown to play an important role in innate and acquired immune responses. In this study, attenuatedErysipelothrix rhusiopathiaestrains were engineered to produce porcine IL-18 (poIL-18) and evaluated for their potential immunostimulatory effect in animals. Recombinant poIL-18 was successfully expressed in the recombinantE. rhusiopathiaestrains YS-1/IL-18 and KO/IL-18. The culture supernatant of YS-1/IL-18 was confirmed to induce IFN-γ production in murine splenocytesin vitro, and this production was inhibited by incubation with anti-poIL-18 monoclonal antibodies. Furthermore, more IFN-γ production was induced upon stimulation of splenocytes with concanavalin A for splenocytes from mice that were intraperitoneally inoculated with YS-1/IL-18 than for splenocytes from control mice inoculated with the parent strain YS-1. Peritoneal macrophages from mice preinoculated with YS-1/IL-18 exhibited enhanced phagocytosis ofSalmonella entericasubsp.entericaserovar Typhimurium compared with peritoneal macrophages from control mice preinoculated with YS-1. We also confirmed the immunostimulatory effect on humoral immune responses against antigens ofE. rhusiopathiaeandMycoplasma hyopneumoniaein gnotobiotic pigs that were orally preinoculated with KO/IL-18. Thus, these results provide evidence thatE. rhusiopathiaeis a promising vector for the expression of host cytokines and suggest the potential utility ofE. rhusiopathiaevector-encoded cytokines in the activation of host innate and acquired immune responses.

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An appraisal of survival strategies

Parasitology ◽

10.1017/s0031182000085486 ◽

1984 ◽

Vol 88 (4) ◽

pp. 575-577 ◽

Cited By ~ 1

Author(s):

N. A. Mitchison

Keyword(s):

Immune System ◽

Immune Responses ◽

Survival Strategies ◽

Host Immune System ◽

Cellular Immunology ◽

Host Immune Responses ◽

Host Defence System ◽

Bio Engineering

Only a few years ago parasite immunology looked an unattractive subject better left to the dogged specialists. Parasites and hosts had been playing chess together for a million years, and there seemed little prospect of perturbing matters in favour of the host immune system. All that has changed, for three reasons. Firstly, we have learned how to grow at least some parasites in vitro, and prospects of doing so with others are encouraging. Secondly, progress in cellular immunology has revealed the sort of loopholes in the host defence system which parasites are likely to exploit: we are learning the questions which matter about parasites as antigens. Thirdly, and most importantly, molecular genetics is being brought to bear on parasites: we can now see a real, though long-term, prospect of manufacturing practicable vaccines through bio-engineering, and more immediately it gives us the tools needed to probe the host immune responses in the form of cloned antigens.

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The ability to combine multiple mRNA antigens targeting multiple pathogens simultaneously, and the robust immune responses are confirmed in several clinical studies

10.31219/osf.io/6qksx ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Immune Responses ◽

Clinical Studies ◽

Large Scale ◽

Antigen Expression ◽

Fine Tuning ◽

Cold Chain ◽

Disruptive Technology ◽

Single Shot ◽

Structural Components ◽

Multiple Pathogens

In the last decade, great progress has been made on mRNA vaccines. MRNA vaccines that are well-tolerated and human immunogenic, stable and can be scaled up to hundreds of millions of doses have been produced with advancements in mRNA design, lipid nanoparticles (LNPs) composition and production techniques. The ability to combine multiple mRNA antigens in the same LNP, targeting multiple pathogens simultaneously, the lack of vector immunity, and the robust immune responses confirmed in several clinical studies make mRNA vaccines a disruptive technology that could change the development of vaccines in the coming years. Moreover, as mRNA was recently employed for large-scale vaccination applications, there is still plenty of room for refining and new advances.Ad-vector-based vaccines have also become promising immunization platforms. Ad vectors' structural components can be harnessed and modified for enhanced tropism, efficient transduction, and optimal antigen expression, and the structural components of Ad vaccine vectors can be harnessed and modified for enhanced tropism, effective transduction, and optimal antigen expression. Ad vectors can be readily created and mass-produced on a commercial basis, and their potency and stability make single-shot immunizations viable without using a frozen cold chain. Ad vectors' flexibility and promise for present and future vaccination applications is evidenced by their development against many illnesses.The use of biomaterials and engineering to improve vaccine delivery control has shown promise in boosting vaccination efficiency and fine-tuning the responses induced. Taken together, these vaccine science innovations have the potential to overcome many of the shortcomings in traditional vaccination technology, and they will almost probably play a crucial part in developing future known and novel disease vaccines.

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