scholarly journals Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression

Science ◽  
2014 ◽  
Vol 343 (6175) ◽  
pp. 1246949-1246949 ◽  
Author(s):  
B. P. Fairfax ◽  
P. Humburg ◽  
S. Makino ◽  
V. Naranbhai ◽  
D. Wong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immune ◽  
Immune Activity ◽  
Regulatory Variants

scholarly journals Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Inflammatory Gene Expression ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

scholarly journals No Change, No Life? What We Know about Phase Variation in Staphylococcus aureus

2021 ◽  
Vol 9 (2) ◽  
pp. 244
Author(s):  
Vishal Gor ◽  
Ryosuke L. Ohniwa ◽  
Kazuya Morikawa
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
High Frequency ◽  
Direct Evidence ◽  
Bacterial Species ◽  
Phase Variation ◽  
Opportunistic Pathogen ◽  
Adaptation Strategy ◽  
Innate Immune ◽  
Epigenetic Mechanisms

Phase variation (PV) is a well-known phenomenon of high-frequency reversible gene-expression switching. PV arises from genetic and epigenetic mechanisms and confers a range of benefits to bacteria, constituting both an innate immune strategy to infection from bacteriophages as well as an adaptation strategy within an infected host. PV has been well-characterized in numerous bacterial species; however, there is limited direct evidence of PV in the human opportunistic pathogen Staphylococcus aureus. This review provides an overview of the mechanisms that generate PV and focuses on earlier and recent findings of PV in S. aureus, with a brief look at the future of the field.

scholarly journals Characterization of Host Responses duringPseudomonas aeruginosaAcute Infection in the Lungs and Blood and after Treatment with the Synthetic Immunomodulatory Peptide IDR-1002

2018 ◽  
Vol 87 (1) ◽  
Author(s):  
Kelli Wuerth ◽  
Amy H. Y. Lee ◽  
Reza Falsafi ◽  
Erin E. Gill ◽  
Robert E. W. Hancock
Keyword(s):  
Gene Expression ◽  
Bacterial Resistance ◽  
Lymphocyte Activation ◽  
Lavage Fluid ◽  
Innate Immune ◽  
Microbial Infection ◽  
Content Type ◽  
Innate Defense ◽  
Lung Infections

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen that causes nosocomial pneumonia and infects patients with cystic fibrosis.P. aeruginosalung infections are difficult to treat due to bacterial resistance to antibiotics, and strains with multidrug resistance are becoming more prevalent. Here, we examined the use of a small host defense peptide, innate defense regulator 1002 (IDR-1002), in an acuteP. aeruginosalung infectionin vivo. IDR-1002 significantly reduced the bacterial burden in bronchoalveolar lavage fluid (BALF), as well as MCP-1 in BALF and serum, KC in serum, and interleukin 6 (IL-6) in BALF. Transcriptome sequencing (RNA-Seq) was conducted on lungs and whole blood, and the effects ofP. aeruginosa, IDR-1002, and the combination ofP. aeruginosaand IDR-1002 were evaluated. Differential gene expression analysis showed thatP. aeruginosaincreased multiple inflammatory and innate immune pathways, as well as affected hemostasis, matrix metalloproteinases, collagen biosynthesis, and various metabolism pathways in the lungs and/or blood. Infected mice treated with IDR-1002 had significant changes in gene expression compared to untreated infected mice, with fewer differentially expressed genes associated with the inflammatory and innate immune responses to microbial infection, and treatment also affected morphogenesis, certain metabolic pathways, and lymphocyte activation. Overall, these results showed that IDR-1002 was effective in treatingP. aeruginosaacute lung infections and associated inflammation.

scholarly journals TheC. difficile clnRABoperon initiates adaptations to the host environment in response to LL-37

2018 ◽  
Author(s):  
Emily C. Woods ◽  
Adrianne N. Edwards ◽  
Shonna M. McBride
Keyword(s):  
Gene Expression ◽  
Diarrheal Disease ◽  
Regulatory System ◽  
Innate Immune ◽  
Cellular Transport ◽  
Intestinal Environment ◽  
Host Defense Peptide ◽  
Surface Active ◽  
Pleiotropic Regulator ◽  
Host Signal

ABSTRACTTo cause disease,Clostridioides(Clostridium)difficilemust resist killing by innate immune effectors in the intestine, including the host antimicrobial peptide, cathelicidin (LL-37). The mechanisms that enableC. difficileto adapt to the intestine in the presence of antimicrobial peptides are unknown. Expression analyses revealed an operon,CD630_16170-CD630_16190(clnRAB), which is highly induced by LL-37 and is not expressed in response to other cell-surface active antimicrobials. This operon encodes a predicted transcriptional regulator (clnR) and an ABC transporter system (clnAB), all of which are required for function. Analyses of aclnRmutant indicate that ClnR is a pleiotropic regulator that directly binds to LL-37 and controls expression of numerous genes, including many involved in metabolism, cellular transport, signaling, gene regulation, and pathogenesis. The data suggest that ClnRAB is a novel regulatory mechanism that senses LL-37 as a host signal and regulates gene expression to adapt to the host intestinal environment during infection.Author SummaryC. difficileis a major nosocomial pathogen that causes severe diarrheal disease. ThoughC. difficileis known to inhabit the human gastrointestinal tract, the mechanisms that allow this pathogen to adapt to the intestine and survive host defenses are not known. In this work, we investigated the response ofC. difficileto the host defense peptide, LL-37, to determine the mechanisms underlying host adaptation and survival. Expression analyses revealed a previously unknown locus, which we namedclnRAB, that is highly induced by LL-37 and acts as a global regulator of gene expression inC. difficile. Mutant analyses indicate that ClnRAB is a novel regulatory system that senses LL-37 as a host signal to regulate adaptation to the intestinal environment.

scholarly journals Comparative innate immune gene expression in chicken intestine after in vivo challenge with commensal (Campylobacter) and pathogenic (Salmonella) bacteria

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Ronan Gerard Shaughnessy ◽  
Kieran G. Meade ◽  
Sarah Cahalane ◽  
Brenda Allan ◽  
Carla Reiman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immune ◽  
Immune Gene ◽  
Chicken Intestine ◽  
Immune Gene Expression ◽  
Innate Immune Gene

scholarly journals Identification by microarray of a common pattern of gene expression in intact intestine and cultured intestinal cells exposed to virulent Aeromonas hydrophila isolates

2006 ◽  
Vol 4 (3) ◽  
pp. 381-388
Author(s):  
Samuel L. Hayes ◽  
Bethany R. Lye ◽  
Dennis J. Lye ◽  
Mark R. Rodgers ◽  
Gerard Stelma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aeromonas Hydrophila ◽  
Innate Immune ◽  
Intestinal Cell ◽  
Infection Model ◽  
Common Pattern ◽  
Intestinal Cell Line ◽  
Small Intestinal ◽  
Virulent Aeromonas Hydrophila ◽  
Common Infection

The genus Aeromonas comprises known virulent and avirulent isolates and has been implicated in waterborne disease. A common infection model of human gastroenteritis associated with A. hydrophila uses neonatal mice. The goal of this research was to evaluate whether a murine small intestinal cell line could provide comparable results to the gene expression changes in the neonatal mouse model. Changes in mRNA expression in host cell cultures and intestinal tissues were measured after exposure to virulent Aeromonas hydrophila strains. A. hydrophila caused the up-regulation of more than 200 genes in neonates and over 50 genes in cell culture. Twenty-six genes were found to be in common between the two models, of which the majority are associated with the innate immune response.

scholarly journals A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity

2021 ◽  
Author(s):  
Alberto Gomez-Carballa ◽  
Irene Rivero-Calle ◽  
Jacobo Pardo-Seco ◽  
Jose Gomez-Rial ◽  
Carmen Rivero-Velasco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Local Level ◽  
Antiviral Response ◽  
Innate Immune ◽  
Nasal Epithelium ◽  
Severe Illness ◽  
Immune Gene ◽  
Innate Antiviral Response ◽  
Immune Related Genes

Background: COVID-19 symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. Methods and findings: We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. We then used a differential expression approach and pathways analysis to detect tissue specific immune severity signals in COVID-19 patients. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were shown in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. Conclusions: We found severity-related signatures in patient tissues mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy.

Sign in / Sign up

Export Citation Format

Share Document