Modulation of Specific and Allergy-Related Immune Responses by Helminths

Helminths are master regulators of host immune responses utilising complex mechanisms to dampen host protective Th2-type responses and favour long-term persistence. Such evasion mechanisms ensure mutual survival of both the parasite and the host. In this paper, we present recent findings on the cells that are targeted by helminths and the molecules and mechanisms that are induced during infection. We discuss the impact of these factors on the host response as well as their effect in preventing the development of aberrant allergic inflammation. We also examine recent findings on helminth-derived molecules that can be used as tools to pinpoint the underlying mechanisms of immune regulation or to determine new anti-inflammatory therapeutics.

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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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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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Enriched LPS Staining within the Germinal Center of a Lymph Node from an HIV-Infected Long-Term Nonprogressor but Not from Progressors

Journal of Immunology Research ◽

10.1155/2020/7471380 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Lei Huang ◽

Jianning Deng ◽

Ren Lang ◽

Guoyang Liao ◽

Wei Jiang

Keyword(s):

Lymph Node ◽

Immune Responses ◽

Lymph Nodes ◽

Germinal Center ◽

Host Response ◽

Microbial Translocation ◽

Collagen Deposition ◽

Immunohistochemistry Staining ◽

Hiv Negative

An increased level of microbial translocation has been observed in HIV-infected individuals. The host response to microbial translocation is compromised in HIV-infected progressors but remains unknown in HIV-infected long-term nonprogressors (LTNPs). To evaluate microbial translocation in HIV, we assessed lipopolysaccharide (LPS) immunohistochemistry staining in lymph nodes. We found enriched bacterial LPS immunohistochemistry staining in the germinal center of a lymph node from an HIV-infected LTNP, evenly distributed from three progressors with impaired germinal center structures and rarely detected from two HIV-negative individuals. The impaired germinal center structures were consistent with collagen deposition in lymph nodes using immunohistochemistry staining. These results suggest greater immune responses against bacterial LPS translocation in LTNPs, which may reveal an important mechanism in controlling microbial translocation and disease progression in HIV LTNPs.

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Probing the Unknowns in Cytokinin-Mediated Immune Defense in Arabidopsis with Systems Biology Approaches

Bioinformatics and Biology Insights ◽

10.4137/bbi.s13462 ◽

2014 ◽

Vol 8 ◽

pp. BBI.S13462 ◽

Cited By ~ 10

Author(s):

Muhammad Naseem ◽

Meik Kunz ◽

Thomas Dandekar

Keyword(s):

Systems Biology ◽

Immune Responses ◽

Protein Interactions ◽

Immune Defense ◽

Immune Functions ◽

Protein Protein Interactions ◽

Cytokinin Signaling ◽

Host Immune Responses ◽

Arabidopsis Protein ◽

Underlying Mechanisms

Plant hormones involving salicylic acid (SA), jasmonic acid (JA), ethylene (Et), and auxin, gibberellins, and abscisic acid (ABA) are known to regulate host immune responses. However, plant hormone cytokinin has the potential to modulate defense signaling including SA and JA. It promotes plant pathogen and herbivore resistance; underlying mechanisms are still unknown. Using systems biology approaches, we unravel hub points of immune interaction mediated by cytokinin signaling in Arabidopsis. High-confidence Arabidopsis protein—protein interactions (PPI) are coupled to changes in cytokinin-mediated gene expression. Nodes of the cellular interactome that are enriched in immune functions also reconstitute sub-networks. Topological analyses and their specific immunological relevance lead to the identification of functional hubs in cellular interactome. We discuss our identified immune hubs in light of an emerging model of cytokinin-mediated immune defense against pathogen infection in plants.

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Established Cotton Stainer Gut Bacterial Mutualists Evade Regulation by Host Antimicrobial Peptides

Applied and Environmental Microbiology ◽

10.1128/aem.00738-19 ◽

2019 ◽

Vol 85 (13) ◽

Cited By ~ 3

Author(s):

Thomas Ogao Onchuru ◽

Martin Kaltenpoth

Keyword(s):

Immune Response ◽

Immune Responses ◽

Target Genes ◽

Quantitative Composition ◽

Bacterial Symbionts ◽

Immune Systems ◽

Host Fitness ◽

Host Immune Responses ◽

Cotton Stainer ◽

The Impact

ABSTRACT Symbioses with microorganisms are ubiquitous in nature and confer important ecological traits to animal hosts but also require control mechanisms to ensure homeostasis of the symbiotic interactions. In addition to protecting hosts against pathogens, animal immune systems recognize, respond to, and regulate mutualists. The gut bacterial symbionts of the cotton stainer bug, Dysdercus fasciatus, elicit an immune response characterized by the upregulation of c-type lysozyme and the antimicrobial peptide pyrrhocoricin in bugs with their native gut microbiota compared to that in dysbiotic insects. In this study, we investigated the impact of the elicited antimicrobial immune response on the established cotton stainer gut bacterial symbiont populations. To this end, we used RNA interference (RNAi) to knock down immunity-related genes hypothesized to regulate the symbionts, and we subsequently measured the effect of this silencing on host fitness and on the abundance of the major gut bacterial symbionts. Despite successful downregulation of target genes by both ingestion and injection of double-stranded RNA (dsRNA), the silencing of immunity-related genes had no effect on either host fitness or the qualitative and quantitative composition of established gut bacterial symbionts, indicating that the host immune responses are not actively involved in the regulation of the nutritional and defensive gut bacterial mutualists. These results suggest that close associations of bacterial symbionts with their hosts can result in the evolution of mechanisms ensuring that symbionts remain insensitive to host immunological responses, which may be important for the evolutionary stability of animal-microbe symbiotic associations. IMPORTANCE Animal immune systems are central for the protection of hosts against enemies by preventing or eliminating successful infections. However, in the presence of beneficial bacterial mutualists, the immune system must strike a balance of not killing the beneficial symbionts while at the same time preventing enemy attacks. Here, using the cotton stainer bug, we reveal that its long-term associated bacterial symbionts are insensitive to the host’s immune effectors, suggesting adaptation to the host’s defenses, thereby strengthening the stability of the symbiotic relationship. The ability of the symbionts to elicit host immune responses but remain insensitive themselves may be a mechanism by which the symbionts prime hosts to fight future pathogenic infections.

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Acquired immune heterogeneity and its sources in human helminth infection

Parasitology ◽

10.1017/s0031182010001216 ◽

2010 ◽

Vol 138 (2) ◽

pp. 139-159 ◽

Cited By ~ 36

Author(s):

C. D. BOURKE ◽

R. M. MAIZELS ◽

F. MUTAPI

Keyword(s):

Immune Responses ◽

Large Scale ◽

Antigen Expression ◽

Epidemiological Studies ◽

Public Health Importance ◽

Host Immune Responses ◽

Parasitic Worm ◽

Acquired Immune Responses ◽

The Impact

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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Host Immune Responses to Chronic Adenovirus Infections in Human and Nonhuman Primates

Journal of Virology ◽

10.1128/jvi.02160-08 ◽

2008 ◽

Vol 83 (6) ◽

pp. 2623-2631 ◽

Cited By ~ 48

Author(s):

Roberto Calcedo ◽

Luk H. Vandenberghe ◽

Soumitra Roy ◽

Suryanarayan Somanathan ◽

Lili Wang ◽

...

Keyword(s):

T Cells ◽

Immune Responses ◽

Peripheral Blood ◽

Neutralizing Antibodies ◽

Potential Role ◽

Low Frequencies ◽

Host Immune Responses ◽

Virus Genomes ◽

The Impact

ABSTRACT Recent studies indicate that great apes and macaques chronically shed adenoviruses in the stool. Shedding of adenovirus in the stool of humans is less prevalent, although virus genomes persist in gut-associated lymphoid tissue in the majority of individual samples. Chimpanzees have high levels of broadly reactive neutralizing antibodies to adenoviruses in serum, with very low frequencies of adenovirus-specific T cells in peripheral blood. A similar situation exists in macaques; sampling of guts from macaques demonstrated adenovirus-specific T cells in lamina propria. Humans show intermediate levels of serum neutralizing antibodies, with adenovirus-specific T cells in peripheral blood of all individuals sampled and about 20% of samples from the gut, suggesting a potential role of T cells in better controlling virus replication in the gut. The overall structure of the E3 locus, which is involved in modulating the host's response to infection, is degenerate in humans compared to that in apes, which may contribute to diminished evasion of host immunity. The impact of adenovirus persistence and immune responses should be considered when using adenoviral vectors in gene therapy and genetic vaccines.

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Protective Efficacy and Long-Term Immunogenicity in Cynomolgus Macaques by Ebola Virus Glycoprotein Synthetic DNA Vaccines

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy537 ◽

2018 ◽

Vol 219 (4) ◽

pp. 544-555 ◽

Cited By ~ 11

Author(s):

Ami Patel ◽

Emma L Reuschel ◽

Kimberly A Kraynyak ◽

Trina Racine ◽

Daniel H Park ◽

...

Keyword(s):

Immune Responses ◽

Ebola Virus ◽

Dna Vaccines ◽

Viral Vector ◽

Protective Efficacy ◽

Lethal Challenge ◽

Virus Glycoprotein ◽

Cynomolgus Macaques ◽

The Impact

Abstract Background There remains an important need for prophylactic anti-Ebola virus vaccine candidates that elicit long-lasting immune responses and can be delivered to vulnerable populations that are unable to receive live-attenuated or viral vector vaccines. Methods We designed novel synthetic anti-Ebola virus glycoprotein (EBOV-GP) DNA vaccines as a strategy to expand protective breadth against diverse EBOV strains and evaluated the impact of vaccine dosing and route of administration on protection against lethal EBOV-Makona challenge in cynomolgus macaques. Long-term immunogenicity was monitored in nonhuman primates for >1 year, followed by a 12-month boost. Results Multiple-injection regimens of the EBOV-GP DNA vaccine, delivered by intramuscular administration followed by electroporation, were 100% protective against lethal EBOV-Makona challenge. Impressively, 2 injections of a simple, more tolerable, and dose-sparing intradermal administration followed by electroporation generated strong immunogenicity and was 100% protective against lethal challenge. In parallel, we observed that EBOV-GP DNA vaccination induced long-term immune responses in macaques that were detectable for at least 1 year after final vaccination and generated a strong recall response after the final boost. Conclusions These data support that this simple intradermal-administered, serology-independent approach is likely important for additional study towards the goal of induction of anti-EBOV immunity in multiple at-risk populations.

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Bisphenol A, S or F mother’s dermal impregnation impairs offspring immune responses in a dose and sex-specific manner in mice

Scientific Reports ◽

10.1038/s41598-021-81231-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yann Malaisé ◽

Corinne Lencina ◽

Christel Cartier ◽

Maïwenn Olier ◽

Sandrine Ménard ◽

...

Keyword(s):

Immune Responses ◽

Perinatal Exposure ◽

Immune Markers ◽

Offspring Sex ◽

Structural Analogues ◽

Specific Manner ◽

Long Term Consequences ◽

The Impact ◽

First Time

AbstractBisphenol (BP)A is an endocrine disruptor (ED) widely used in thermal papers. Regulatory restrictions have been established to prevent risks for human health, leading to BPA substitution by structural analogues, like BPS and BPF. We previously demonstrated that oral perinatal exposure to BPA had long-term consequences on immune responses later in life. It appears now essential to enhance our understanding on immune impact of different routes of BP exposure. In this study, we aimed at comparing the impact of mother dermal exposure to BPs on offspring immune system at adulthood. Gravid mice were dermally exposed to BPA, BPS or BPF at 5 or 50 μg/kg of body weight (BW)/day (d) from gestation day 15 to weaning of pups at post-natal day (PND)21. In offspring, BPs dermal impregnation of mothers led to adverse effects on immune response at intestinal and systemic levels that was dependent on the BP, the dose and offspring sex. These findings provide, for the first time, results on long-term consequences of dermal perinatal BPs exposure on immune responses in offspring. This work warns that it is mandatory to consider immune markers, dose exposure as well as sex in risk assessment associated with new BPA’s alternatives.

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Obesity Correlates With Pronounced Aberrant Innate Immune Responses in Hospitalized Aged COVID-19 Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.760288 ◽

2021 ◽

Vol 12 ◽

Author(s):

Michael Z. Zulu ◽

Suhas Sureshchandra ◽

Amanda N. Pinski ◽

Brianna Doratt ◽

Weining Shen ◽

...

Keyword(s):

Immune Responses ◽

Host Response ◽

Immune Cell ◽

Severe Disease ◽

Low Grade ◽

Igg Antibody ◽

Aged Patients ◽

Prevalence Of Obesity ◽

Antibody Titers ◽

The Impact

Both age and obesity are leading risk factors for severe coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, although most infections occur in individuals under the age of 55 years, 95% of hospitalizations, admissions to the intensive care unit, and deaths occur in those over the age of 55 years. Moreover, hospitalized COVID-19 patients have a higher prevalence of obesity. It is generally believed that chronic low-grade inflammation and dysregulated innate and adaptive immune responses that are associated with aging and obesity are responsible for this elevated risk of severe disease. However, the impact of advanced age and obesity on the host response to SARS-CoV-2 infection remains poorly defined. In this study, we assessed changes in the concentration of soluble immune mediators, IgG antibody titers, frequency of circulating immune cells, and cytokine responses to mitogen stimulation as a function of BMI and age. We detected significant negative correlations between BMI and myeloid immune cell subsets that were more pronounced in aged patients. Similarly, inflammatory cytokine production by monocytes was also negatively correlated with BMI in aged patients. These data suggest that the BMI-dependent impact on host response to SARS-CoV-2 is more pronounced on innate responses of aged patients.

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