scholarly journals Royal decree: gene expression in transgenerationally immune primed bumblebee workers mimics a primary immune response

2016 ◽  
Author(s):  
Seth M Barribeau ◽  
Paul Schmid-Hempel ◽  
Ben M Sadd
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Immune System ◽  
Primary Immune Response ◽  
Receptor Protein ◽  
Immune Memory ◽  
Individual Response ◽  
Beta Glucan ◽  
Royal Decree ◽  
Immune Priming

Invertebrates lack the cellular and physiological machinery of the adaptive immune system, but show specificity in their immune response [1, 2] and immune priming [3-11]. Functionally, immune priming is comparable to immune memory in vertebrates. Individuals that have survived exposure to a given parasite are better protected against subsequent exposures. Protection may be cross-reactive (e.g. [12]), but demonstrations of persistent and specific protection in invertebrates are increasing [3, 5]. This immune priming can cross generations ("trans-generational" immune priming) [4, 8], preparing offspring for the prevailing parasite environment. While these phenomena gain increasing support, the mechanistic foundations underlying such immune priming, both within and across generations, remain largely unknown. Using a transcriptomic approach, we show a bacterial challenge to bumblebee queens, known to induce trans-generational immune priming, alters daughter (worker) gene expression. Daughters, even when unchallenged themselves, constitutively express a core set of the genes induced upon direct bacterial exposure, including high expression of antimicrobial peptides, a beta-glucan receptor protein implicated in bacterial recognition and the induction of the toll signaling pathway[13], and slit-3 which is important in honeybee immunity[14]. Maternal challenge results in a distinct upregulation of their daughters' immune system, with a signature overlapping with the induced individual response to a direct immune challenge. This will mediate mother-offspring protection, but also associated costs related to reconfiguration of constitutive immune expression. Identification of conserved immune pathways in memory-like responses has important implications for our understanding of the innate immune system, including the innate components in vertebrates, which share many of these pathways[15].

scholarly journals Immune stimulation reduces sleep and memory ability in Drosophila melanogaster

2014 ◽  
Author(s):  
Eamonn B Mallon ◽  
Akram Alghamdi ◽  
Robert T.K. Holdbrook ◽  
Ezio Rosato
Keyword(s):  
Immune Response ◽  
Drosophila Melanogaster ◽  
Immune System ◽  
Receptor Protein ◽  
Immune Stimulation ◽  
Night Sleep ◽  
Conditioning Paradigm ◽  
Memory Ability ◽  
Neural Interactions ◽  
Aversive Classical Conditioning

Psychoneuroimmunology studies the increasing number of connections between neurobiology, immunology and behaviour. We establish Drosophila melanogaster as a tractable model in this field by demonstrating the effects of the immune response on two fundamental behaviours: sleep and memory ability. We used the Geneswitch system to upregulate peptidoglycan receptor protein (PGRP) expression, thereby stimulating the immune system in the absence of infection. Geneswitch was activated by feeding the steroid RU486, to the flies. We used an aversive classical conditioning paradigm to quantify memory and measures of activity to infer sleep. Immune stimulated flies exhibited reduced levels of sleep, which could not be explained by a generalised increase in waking activity. The effects on sleep were more pronounced for day compared to night sleep. Immune stimulated flies also showed a reduction in memory abilities. These results establish Drosophila as a model for immune-neural interactions and suggest a possible role for sleep in the interplay between the immune response and memory.

TLR2-mediated innate immune priming boosts lung anti-viral immunity

2020 ◽  
pp. 2001584
Author(s):  
Jason Girkin ◽  
Su-Ling Loo ◽  
Camille Esneau ◽  
Steven Maltby ◽  
Francesca Mercuri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immunity ◽  
Viral Load ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Immune Priming ◽  
Tlr2 Activation

Research questionAssessment of whether TLR2 activation boosts the innate immune response to rhinovirus infection, as a treatment strategy for virus-induced respiratory diseases.MethodsWe employed treatment with a novel TLR2 agonist (INNA-X) prior to rhinovirus infection in mice, and INNA-X treatment in differentiated human bronchial epithelial cells derived from asthmatic-donors. We assessed viral load, immune cell recruitment, cytokines, type I and III IFN production, as well as the lung tissue and epithelial cell immune transcriptome.ResultsWe show in vivo, that a single INNA-X treatment induced innate immune priming characterised by low-level IFN-λ, Fas ligand, chemokine expression and airway lymphocyte recruitment. Treatment 7-days before infection significantly reduced lung viral load, increased IFN-β/λ expression and inhibited neutrophilic inflammation. Corticosteroid treatment enhanced the anti-inflammatory effects of INNA-X. Treatment 1-day before infection increased expression of 190 lung tissue immune genes. This tissue gene expression signature was absent with INNA-X treatment 7-days before infection, suggesting an alternate mechanism, potentially via establishment of immune cell-mediated mucosal innate immunity. In vitro, INNA-X treatment induced a priming response defined by upregulated IFN-λ, chemokine and anti-microbial gene expression that preceded an accelerated response to infection enriched for NF-κB-regulated genes and reduced viral loads, even in epithelial cells derived from asthmatic donors with intrinsic delayed anti-viral immune response.ConclusionAirway epithelial cell TLR2 activation induces prolonged innate immune priming, defined by early NF-κB activation, IFN-λ expression and lymphocyte recruitment. This response enhanced anti-viral innate immunity and reduced virus-induced airway inflammation.

scholarly journals Immune stimulation reduces sleep and memory ability in Drosophila melanogaster

2014 ◽  
Author(s):  
Eamonn Mallon ◽  
Akram Alghamdi ◽  
Robert Holdbrook ◽  
Ezio Rosato
Keyword(s):  
Immune Response ◽  
Drosophila Melanogaster ◽  
Immune System ◽  
Receptor Protein ◽  
Immune Stimulation ◽  
Night Sleep ◽  
Conditioning Paradigm ◽  
Memory Ability ◽  
Neural Interactions ◽  
Aversive Classical Conditioning

Psychoneuroimmunology studies the increasing number of connections between neurobiology, immunology and behaviour. We establish Drosophila melanogaster as a tractable model in this field by demonstrating the effects of the immune response on two fundamental behaviours: sleep and memory ability. We used the Geneswitch system to upregulate peptidoglycan receptor protein (PGRP) expression, thereby stimulating the immune system in the absence of infection. Geneswitch was activated by feeding the steroid RU486, to the flies. We used an aversive classical conditioning paradigm to quantify memory and measures of activity to infer sleep. Immune stimulated flies exhibited reduced levels of sleep, which could not be explained by a generalised increase in waking activity. The effects on sleep were more pronounced for day compared to night sleep. Immune stimulated flies also showed a reduction in memory abilities. These are important results as they establish Drosophila as a model for immune-neural interactions and provide a possible role for sleep in the interplay between the immune response and memory.

scholarly journals Molecular Insights of Immune Responses Variability in COVID-19 Patients: A Review

2021 ◽  
Vol 10 (3) ◽  
pp. 2402-2413
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Inflammatory Response ◽  
Clinical Symptoms ◽  
Multiorgan Failure ◽  
Innate Immune ◽  
Immune Memory ◽  
System Response ◽  
The Difference ◽  
Novel Coronavirus

Currently, a novel coronavirus disease 2019 (COVID 19) caused by SARS-CoV-2 has emerged worldwide. This chronic viral infection causes an acute respiratory distress syndrome (ARDS) which its pathophysiology is not yet well elucidated. However, ARDS has shown that ARDS causes diffuse alveolar damages induced by an excessive inflammatory response and a lack of anti-inflammatory response to the virus. Furthermore, these pathophysiological characteristics are associated with multiorgan failure and can increase the mortality rate. The difference in immune system response against COVID-19 is not well known. However, variability in innate immune system receptors between patients infected with SARS-CoV-2 as a function of aging and sex can explain this difference. Thus, innate immune memory or trained immunity mediated by epigenetic mechanisms is also involved in the variability response against COVID-19. The action of an adaptative immune response, in particular, antigen presentation via HLA is also a key element in this variability. Finally, each viral strain's capacity in evading the action of the immune response has also been suggested as an important mechanism by which certain patients infected with SARS-CoV-2 develop severity and others did not develop any clinical symptoms.

scholarly journals Experimental evolution of immunological specificity

2019 ◽  
Vol 116 (41) ◽  
pp. 20598-20604 ◽  
Author(s):  
Kevin Ferro ◽  
Robert Peuß ◽  
Wentao Yang ◽  
Philip Rosenstiel ◽  
Hinrich Schulenburg ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
High Specificity ◽  
Immune Memory ◽  
Transcriptomic Response ◽  
Immune Priming ◽  
Immune Genes ◽  
Adaptive Immune ◽  
Immunological Specificity ◽  
Invertebrate Model

Memory and specificity are hallmarks of the adaptive immune system. Contrary to prior belief, innate immune systems can also provide forms of immune memory, such as immune priming in invertebrates and trained immunity in vertebrates. Immune priming can even be specific but differs remarkably in cellular and molecular functionality from the well-studied adaptive immune system of vertebrates. To date, it is unknown whether and how the level of specificity in immune priming can adapt during evolution in response to natural selection. We tested the evolution of priming specificity in an invertebrate model, the beetle Tribolium castaneum. Using controlled evolution experiments, we selected beetles for either specific or unspecific immune priming toward the bacteria Pseudomonas fluorescens, Lactococcus lactis, and 4 strains of the entomopathogen Bacillus thuringiensis. After 14 generations of host selection, specificity of priming was not universally higher in the lines selected for specificity, but rather depended on the bacterium used for priming and challenge. The insect pathogen B. thuringiensis induced the strongest priming effect. Differences between the evolved populations were mirrored in the transcriptomic response, revealing involvement of immune, metabolic, and transcription-modifying genes. Finally, we demonstrate that the induction strength of a set of differentially expressed immune genes predicts the survival probability of the evolved lines upon infection. We conclude that high specificity of immune priming can evolve rapidly for certain bacteria, most likely due to changes in the regulation of immune genes.

scholarly journals Time-Resolved Gene Expression Analysis Monitors the Regulation of Inflammatory Mediators and Attenuation of Adaptive Immune Response by Vitamin D

2022 ◽  
Vol 23 (2) ◽  
pp. 911
Author(s):  
Andrea Hanel ◽  
Carsten Carlberg
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Immune Response ◽  
Immune System ◽  
Calcium Binding ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Adaptive Immune Response ◽  
Time Resolved ◽  
Adaptive Immune

Peripheral blood mononuclear cells (PBMCs) belong to the innate and adaptive immune system and are highly sensitive and responsive to changes in their systemic environment. In this study, we focused on the time course of transcriptional changes in freshly isolated human PBMCs 4, 8, 24 and 48 h after onset of stimulation with the active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Taking all four time points together, 662 target genes were identified and segregated either by time of differential gene expression into 179 primary and 483 secondary targets or by driver of expression change into 293 direct and 369 indirect targets. The latter classification revealed that more than 50% of target genes were primarily driven by the cells' response to ex vivo exposure than by the nuclear hormone and largely explained its down-regulatory effect. Functional analysis indicated vitamin D’s role in the suppression of the inflammatory and adaptive immune response by down-regulating ten major histocompatibility complex class II genes, five alarmins of the S100 calcium binding protein A family and by affecting six chemokines of the C-X-C motif ligand family. Taken together, studying time-resolved responses allows to better contextualize the effects of vitamin D on the immune system.

scholarly journals T cell thymic selection and peripheral homeostatic proliferation in infectious diseases

2020 ◽  
Vol 9 (5-6) ◽  
pp. 629-638
Author(s):  
V. A. Kozlov
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Acute Infection ◽  
Infectious Agent ◽  
Primary Immune Response ◽  
Homeostatic Proliferation ◽  
Main Function ◽  
Infectious Process ◽  
Chronic Course

There is no doubt that infectious agents and host undergo multilayered yet not fully understood interactions. This is primarily due to at least mechanisms resulting in chronic course of infectious process. Acute infection proceeds in parallel with primary immune response and its typical phases, each of which manifests as certain stage in clinical picture featured with disease onset and subsequent recovery. A whole process of immune response developing against infectious agent occurs in peripheral lymphoid organs and immune tissues. With regard to the role of immune system in infectious process, process, two main outstanding issues still remain unanswered: 1) what are the mechanisms of host death in the case of acute infectious process? 2) what is a “fault” of immune system in it? In its inferiority or in abruptly suppressed functions induced by infectious agent, when it “does not have time” to mount an immune response of sufficient power? So far, no answer is still found yet. The second question concerns mechanisms of converting to chronic course of infectious process. The obtained available in publications evidence about an intimately involved thymus as the central immune organ in infectious process of, the main function of which is to ensure developing central immune tolerance to self-antigens accomplished via T-cell positive and negative selection. It turned out that in case of some examined infections due to pathogens, which entered the thymus, such intimate events such as partial tolerance to pathogens and autoimmune reactivity are altered. Moreover, these processes are further aggravated by homeostatic proliferation, which is also induced by an infectious agent. In both cases, it accounts for decreased magnitude of immune response against a certain pathogen, burdened by emergence of autoimmune reactions.

Methods of Studying Human Dendritic Cells Applicable to Assessing Vaccine Efficacy

2021 ◽  
pp. 87-94
Author(s):  
VYu Talayev ◽  
MV Svetlova ◽  
IY Zaichenko ◽  
ON Babaykina ◽  
EV Voronina
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune System ◽  
Quantitative Methods ◽  
Effective Means ◽  
Dendritic Cell Maturation ◽  
Primary Immune Response ◽  
Human Immune System ◽  
Human Dendritic Cells

Introduction: Vaccines are one of the most effective means of preventing infectious diseases. Their effectiveness and safety are guaranteed by studies of vaccine properties, during their development and during the mandatory preclinical and clinical trials of each new vaccine. Additional information on the mechanisms of vaccine action on human immune system cells can be obtained using in vitro immune response models. The objective of the study was to determine applicability of certain methods of studying human dendritic cells in vitro to assessing the effect of vaccines. Dendritic cells are the most active antigen presenting cells, which play a key role in triggering a primary immune response to an infection or vaccine. Materials and methods: We studied the effect of vaccines on the maturation of dendritic cells, their phagocytic activity and the ability to stimulate T-lymphocytes in vitro. Results: To test the methods, we used vaccines with a known pattern of action on the immune system. All the vaccines induced the expression of dendritic cell maturation markers. At the same time, different vaccines induced a different set of markers and the degree of expression of these molecules. Quantitative methods for assessing phagocytosis and stimulating activity of dendritic cells are described. Conclusion: Methods for evaluation of phagocytosis, phenotypic maturation and functional properties of dendritic cells have been shown to be useful for evaluation of vaccine action. In our opinion, these methods, as a complement to traditional methods for evaluating the immune response, can be used to investigate the action of prototype vaccines at the stage of their development and preclinical trials.

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