Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HIV and innate immunity - a genomics perspective.

ABSTRACT: Innate immunity is a theme of increasing interest for HIV research. However, the term is overstretched to cover biological barriers, cellular systems, soluble factors, signaling pathways, and effectors and is inconsistently applied. A clearer semantic classification of the components of innate immunity is needed, which will have direct relevance to the interpretation of human genome variation. Here, we discuss genomic approaches that can assist in re-defining the perimeter of innate immunity. We place particular emphasis on the characteristics of effectors of the intracellular defense against HIV and other pathogens.

SUBMITTER: Rausell A

PROVIDER: S-EPMC3732074 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

HIV and innate immunity - a genomics perspective.

Rausell Antonio A McLaren Paul J PJ Telenti Amalio A

F1000prime reports 20130801

Innate immunity is a theme of increasing interest for HIV research. However, the term is overstretched to cover biological barriers, cellular systems, soluble factors, signaling pathways, and effectors and is inconsistently applied. A clearer semantic classification of the components of innate immunity is needed, which will have direct relevance to the interpretation of human genome variation. Here, we discuss genomic approaches that can assist in re-defining the perimeter of innate immunity. We ...[more]

PMID: 23967380

Similar Datasets

Targeting Innate Immunity to Combat Cutaneous Stress: The Vitiligo Perspective.

Project description:Multiple factors are involved in the process leading to melanocyte loss in vitiligo including environmental triggers, genetic polymorphisms, metabolic alterations, and autoimmunity. This review aims to highlight current knowledge on how danger signals released by stressed epidermal cells in a predisposed patient can trigger the innate immune system and initiate a cascade of events leading to an autoreactive immune response, ultimately contributing to melanocyte disappearance in vitiligo. We will explore the genetic data available, the specific role of damage-associated-molecular patterns, and pattern-recognition receptors, as well as the cellular players involved in the innate immune response. Finally, the relevance of therapeutic strategies targeting this pathway to improve this inflammatory and autoimmune condition is also discussed.

| S-EPMC8079779 | biostudies-literature

Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases.

Project description:OBJECTIVES:We assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. METHODS:We obtained large-scale genome-wide association study (GWAS) summary statistics from Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). We used multiple sclerosis (MS), an autoimmune disease of the central nervous system, as a positive control. We applied stratified LD score regression to determine if functional marks for cell type and tissue activity, and gene-set lists were enriched for genetic heritability. We compared our results to those from two gene-set enrichment methods (Ingenuity Pathway Analysis and enrichr). RESULTS:There were no significant heritability enrichments for annotations marking genes active within brain regions, but there were significant heritability enrichments for annotations marking genes active within cell types that form part of both the innate and adaptive immune systems. We found this for MS (as expected) and also for AD and PD. The strongest signals were from the adaptive immune system (e.g., T cells) for PD, and from both the adaptive (e.g., T cells) and innate (e.g., CD14: a marker for monocytes, and CD15: a marker for neutrophils) immune systems for AD. Annotations from the liver were also significant for AD. Pathway analysis provided complementary results. INTERPRETATION:For AD and PD, we found significant enrichment of heritability in annotations marking gene activity in immune cells.

| S-EPMC5224821 | biostudies-literature

Thiazolides Elicit Anti-Viral Innate Immunity and Reduce HIV Replication.

Project description:Nitazoxanide (Alinia(®), NTZ) and tizoxanide (TIZ), its active circulating metabolite, belong to a class of agents known as thiazolides (TZD) endowed with broad anti-infective activities. TIZ and RM-4848, the active metabolite of RM-5038, were shown to stimulate innate immunity in vitro. Because natural resistance to HIV-1 infection in HIV-exposed seronegative (HESN) individuals is suggested to be associated with strong innate immune responses, we verified whether TIZ and RM-4848 could reduce the in vitro infectiousness of HIV-1. Peripheral blood mononuclear cells (PBMCs) from 20 healthy donors were infected in vitro with HIV-1BaL in the presence/absence of TIZ or RM4848. HIV-1 p24 were measured at different timepoints. The immunomodulatory abilities of TZD were evaluated by the expression of type I IFN pathway genes and the production of cytokines and chemokines. TZD drastically inhibited in vitro HIV-1 replication (>87%). This was associated with the activation of innate immune responses and with the up-regulation of several interferon-stimulated genes (ISGs), including those involved in cholesterol pathway, particularly the cholesterol-25 hydroxylase (CH25H). TZD inhibition of HIV-1 replication in vitro could be due to their ability to stimulate potent and multifaceted antiviral immune responses. These data warrant the exploration of TZD as preventive/therapeutic agent in HIV infection.

| S-EPMC4890011 | biostudies-other

Identification of innate immunity genes and pathways using a comparative genomics approach.

Project description:To reveal regulators of innate immunity, we used RNAi assays to monitor the immune response when genes are inhibited in Caenorhabditis elegans and mouse macrophages. Genes that altered innate immune responsiveness in C. elegans were validated in murine macrophages, resulting in the discovery of 11 genes that regulate the innate immune response in both systems and the subsequent identification of a protein interaction network with a conserved role in innate immunity regulation. We confirmed the role of four of these 11 genes in antimicrobial gene regulation using available mutants in C. elegans. Several of these genes (acy-1, tub-2, and tbc-1) also regulate susceptibility to the pathogen Pseudomonas aeruginosa. These genes may prove critical to understanding host defense and represent potential therapeutic targets for infectious and immunological diseases.

| S-EPMC2383967 | biostudies-literature

Latent HIV infection disrupts cell-intrinsic innate immunity

Project description:Bulk RNA Sequencing of Jurkat E6-1 & JLat9.2 CD4+ T cells Treated with 100IU/mL IFNb

2022-05-01 | GSE174380 | GEO

Vitally important - does early innate immunity predict recruitment and adult innate immunity?

Project description:The immune system is one of the most important adaptations that has evolved to protect animals from a wide range of pathogens they encounter from early life onwards. During the early developmental period this is particularly true for the innate immunity, as other components of the immune system are, as yet, poorly developed. But innate immunity may not only be crucial for early life survival, but may also have long-lasting effects, for example if early life immunity reflects the functioning of the immune system as a whole. For this reason, we investigated the importance of four constitutive innate immune parameters (natural antibodies, complement activity, concentrations of haptoglobin, and concentrations of nitric oxide) for recruitment in free-living great tits. We compared nestling immunity of recruits with nestling immunity of their nonrecruited siblings. We also investigated within individual consistency of these innate immune parameters for those individuals that recruited, which may be taken as a measure of immune capacity. In accordance with previous studies, we found a clear effect of tarsus length and a trend for body mass on the likelihood to recruit. Nevertheless, we found no evidence that higher levels of constitutive innate immunity as a nestling facilitated local recruitment. Furthermore, individual innate immunity was not consistent across life stages, that is to say, nestling immune parameters did not determine, or respectively, reflect adult innate immune parameters. This plasticity in innate immune components may explain why we did not find long-lasting survival benefits.

| S-EPMC4759050 | biostudies-other

Innate immunity.

Project description:Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease.

| S-EPMC2832725 | biostudies-literature

A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells

Project description:Dendritic cells (DC) serve a key function in host defense, linking innate detection of microbes to the activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of HIV-1 by host innate pattern-recognition receptors and subsequent coupling to antiviral T cell responses is not yet known. DC are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. We show here that, when DC resistance to infection is circumvented, HIV-1 induces DC maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly-synthesized HIV-1 capsid (CA) with cellular cyclophilin A (CypA) and the subsequent activation of the transcription factor IRF3. Because the peptidyl-prolyl isomerase CypA also interacts with CA to promote HIV-1 infectivity, our results suggest that CA conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell intrinsic sensor for HIV-1 exists in DC and mediates an antiviral immune response, but it is not typically engaged due to absence of DC infection. The virulence of HIV-1 may be related to evasion of this response, whose manipulation may be necessary to generate an effective HIV-1 vaccine. We analyzed the gene expression profiles of uninfected human monocyte-derived dendritic cells (MDDCs) and MDDCs infected with an envelope-defective GFP-encoding VSV-G-pseudotyped HIV-1 vector (HIVGFP(G)) and with VSV-G pseudotyped virus-like particles derived from SIVmac to deliver Vpx (SIVVLP(G)), alone or in combination. Cells were infected at day 4 of differentiation and cells were harvested 48 hours later. RNA was extracted with TRIzol. RNA was labeled and hybridized to Human Genome U133A 2.0 arrays arrays following the Affymetrix protocols. Data were analyzed in R and Bioconductor.

2010-09-09 | E-GEOD-22589 | biostudies-arrayexpress

Mitochondria in innate immunity.

Project description:Mitochondria are cellular organelles involved in host-cell metabolic processes and the control of programmed cell death. A direct link between mitochondria and innate immune signalling was first highlighted with the identification of MAVS-a crucial adaptor for RIGI-like receptor signalling-as a mitochondria-anchored protein. Recently, other innate immune molecules, such as NLRX1, TRAF6, NLRP3 and IRGM have been functionally associated with mitochondria. Furthermore, mitochondrial alarmins-such as mitochondrial DNA and formyl peptides-can be released by damaged mitochondria and trigger inflammation. Therefore, mitochondria emerge as a fundamental hub for innate immune signalling.

| S-EPMC3166463 | biostudies-other

Latent HIV infection disrupts cell-intrinsic innate immunity [scRNA-seq]

Project description:Single Cell RNA Sequencing in Primary CD4 T-Cells infected with HIV, suppressed with ART, and treated with IFNb

2022-06-01 | GSE176386 | GEO