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Allergens Elicit an Antiviral Signature in Dendritic Cells

ABSTRACT: Allergens Elicit an Antiviral Signature in Dendritic Cells

PROVIDER: PRJNA755636 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15502153_1.fastq.gz	Fastqsanger.gz
	SRR15502153_2.fastq.gz	Fastqsanger.gz
	SRR15502154_1.fastq.gz	Fastqsanger.gz
	SRR15502154_2.fastq.gz	Fastqsanger.gz
	SRR15502155_1.fastq.gz	Fastqsanger.gz

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Allergens Elicit an Antiviral Signature in Dendritic Cells

Project description:This study compares the transcriptomic changes induced by three distinct aeroallergens in a dendritic cell line with the goal of finding similarities in the response at the gene expression level. Using RNA sequencing of DC2.4 cells, we find that house dust mite, cat hair and timothy grass allergen extracts all induce what appears to be an antiviral genetic signature despite the lack of any viral components in each allergen. Such information may be useful in trying to design therapeutics or interventions for allergic responses which could be effective for multiple allergens despite differences in source and structure.

2021-08-20 | GSE182277 | GEO

Expression data from lung CD11b+ conventional dendritic cells in the steady-state and following exposure to house dust mite allergens

Project description:Using mouse lung resident conventional CD11b+ dendritic cells (CD11b+ cDCs) in the context of house-dust mite (HDM)-driven allergic airway sensitization as a model, we aimed here to identify transcriptional events regulating the pro-Th2 activity of cDCs. We used microarray analyses to identify genes differentially expressed by lung CD11b+ conventional dendritic cells in response to house dust mite allergens in wild-type and Irf3-deficient mice

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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.

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Project description:Analysis of the host response to dengue virus at gene expression level. The hypothesis tested in the present study was that dengue virus triggers and regulate different pathaway with different kinetics controlling the antiviral, the inflammatory and the apoptotic response in primary human DC. Results provide important information of the response to DC to dengue virus showing that antioxidant genes are early stimulated after denv infection reflecting an early production of reactive oxygen species. Interestingely, we demonstrated that ROS production and antiviral and apoptotic responses intersect since chemical inhibition of ROS impairs antiviral and apoptotic responses in these cells. Total RNA obtained from in vitro dengue infected primary human dendritic cells at 0, 6, 12, 18, 24 hours compared to uninfected cells at time 0

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Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles.

Project description:Anaphylactic reactions are triggered when allergens enter the blood circulation and activate immunoglobulin E (IgE)-sensitized mast cells (MCs), causing systemic discharge of prestored proinflammatory mediators. As MCs are extravascular, how they perceive circulating allergens remains a conundrum. Here, we describe the existence of a CD301b+ perivascular dendritic cell (DC) subset that continuously samples blood and relays antigens to neighboring MCs, which vigorously degranulate and trigger anaphylaxis. DC antigen transfer involves the active discharge of surface-associated antigens on 0.5- to 1.0-micrometer microvesicles (MVs) generated by vacuolar protein sorting 4 (VPS4). Antigen sharing by DCs is not limited to MCs, as neighboring DCs also acquire antigen-bearing MVs. This capacity of DCs to distribute antigen-bearing MVs to various immune cells in the perivascular space potentiates inflammatory and immune responses to blood-borne antigens.

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Project description:The current SARS-CoV-2/COVID-19 pandemic causes medical and socioeconomic havoc. Despite the availability of vaccines, cost-effective treatment options preventing morbidity and mortality are urgently needed. To identify affordable, ubiquitously available, and effective treatments, we tested herbs consumed worldwide as herbal teas regarding their antiviral activity against SARS-CoV-2. Aqueous infusions prepared by boiling leaves of the Lamiaceae perilla and sage elicit potent and sustained antiviral activity against SARS-CoV-2 in therapeutic as well as prophylactic regimens. The herbal infusions exerted antiviral effects comparable to interferon-β and remdesivir but outperformed convalescent sera and interferon-α2 upon short-term treatment early after infection. Based on protein fractionation analyses, we identified caffeic acid, perilla aldehyde, and perilla alcohol as antiviral compounds. Global mass-spectrometry (MS) analyses performed comparatively in two different infection models (Vero E6 and Caco-2 cell lines) revealed changes of the proteome upon treatment with herbal infusions and provided insights into the mode of action. As inferred by the MS data, induction of heme oxygenase 1 (HMOX-1) was confirmed as effector mechanism by the antiviral activity of HMOX-1-inducing compounds sulforaphane and fraxetin. In conclusion, herbal teas based on perilla and sage exhibit antiviral activity against SARS-CoV-2 including the variants of concern Alpha, Beta, Delta, and Omicron.

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Gene expression data from human myeloid dendritic cells stimulated with peanut protein and other allergens

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A developing HPA axis permits neonatal immune sensitivity to common allergens [scRNA-Seq]

Project description:Atopic and allergic diseases predominantly manifest in early life, a period of profound growth and maturation. Yet, there is a dearth of information on the impact of developmental parameters on the neonatal immune reaction to allergens. Here we demonstrate that common allergens including house dust mite (HDM) elicited potent type 17 inflammatory responses from neonatal but not adult mice. HDM-induced inflammation was abolished in Rorgt-, gd T cell-, or epithelial IL-17RC- deficient animals and surprisingly did not require nociceptors or lymph node engagement. Instead, neonatal CD301b+ type 2 conventional dendritic cells (cDC2s) abundantly engulfed allergen and locally activated gd T cells in the skin. Despite uptaking equivalent antigen to neonates, adult cDC2s did not promiscuously activate in the skin. Mechanistically, this discrepancy was not attributable to cell-intrinsic differences arising from the distinct developmental origins of neonatal and adult cDC2s. Instead, neonatal cDC2 hyperactivation could be traced to a lower systemic glucocorticoid level, a consequence of an immature hypothalamic-pituitary-adrenal (HPA) axis in early life, and could be reversed by cortisol administration at the time of allergen challenge. These findings bring to fore the influence of organismal developmental factors in shaping immune sensitivity to allergens in early life.

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