scholarly journals Induction of transposable element expression is central to innate sensing

2021 ◽  
Author(s):  
Derek C. Rookhuizen ◽  
Pierre-Emmanuel Bonte ◽  
Mengliang Ye ◽  
Thomas Hoyler ◽  
Matteo Gentili ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Physiological Responses ◽  
Influenza Virus Infection ◽  
Innate Immune ◽  
Type I ◽  
Dna Sensor ◽  
Histone 3 ◽  
Molecular Pattern ◽  
Pathogen Associated Molecular Pattern

SUMMARYEvidence indicates that transposable elements (TEs) stimulate innate sensing pathways in various pathologies but it is not clear whether they are sensed during normal physiological responses. Here we show that, during activation with an exogenous pathogen associated molecular pattern (PAMP), dendritic cells (DCs) epigenetically remodel heterochromatin at TEs by depleting the methyltransferase Suv39h1 and reducing histone-3 lysine-9 trimethylation (H3K9me3). TLR4 signaling activates TE expression to enhance innate responses through the DNA sensor cGAS. Cytosolic cGAS-bound DNA comprised LINE1 TEs as the predominant endogenous ligands. Concordantly, LINE1 inhibition attenuated the type-I IFN response to LPS and rescued influenza virus infection. We propose that in healthy cells, exogenous PAMPs epigenetically activate self-derived PAMPs (LINE1) that engage cGAS to enhance responses. These data explain why pathogens employ redundant and broad innate immune countermeasures, to suppress activation of host PAMPs and illustrate a hitherto unappreciated role for host genome-derived PAMPs in response to pathogens.

scholarly journals Rapid Differentiation of Monocytes into Type I IFN-Producing Myeloid Dendritic Cells as an Antiviral Strategy against Influenza Virus Infection

2012 ◽  
Vol 189 (5) ◽  
pp. 2257-2265 ◽  
Author(s):  
Weiping Cao ◽  
Andrew K. Taylor ◽  
Renata E. Biber ◽  
William G. Davis ◽  
Jin Hyang Kim ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Type I ◽  
Type I Ifn ◽  
Myeloid Dendritic Cells

PLASMACYTOID DENDRITIC CELLS FUNCTION IN HIV INFECTION

2008 ◽  
Vol 31 (4) ◽  
pp. 13
Author(s):  
Martin Hyrcza ◽  
Mario Ostrowski ◽  
Sandy Der
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Hiv Infection ◽  
Gene Transcription ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

scholarly journals Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 456 ◽  
Author(s):  
Philippe Saas ◽  
Alexis Varin ◽  
Sylvain Perruche ◽  
Adam Ceroi
Keyword(s):  
Dendritic Cells ◽  
Lipid Metabolism ◽  
Nuclear Receptors ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Plasmacytoid Dendritic Cell ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Cells ◽  
Immune Functions

There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. Some differences may be related to the origin of PDC (human versus mouse PDC or blood-sorted versus FLT3 ligand stimulated-bone marrow-sorted PDC). The kinetics of glycolysis may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR, explaining a delayed glycolysis. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statins or LXR agonists) in these cells. Finally, lipid-activated nuclear receptors (i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role.

scholarly journals Dendritic Cells Targeting Lactobacillus plantarum Strain NC8 with a Surface-Displayed Single-Chain Variable Fragment of CD11c Induce an Antigen-Specific Protective Cellular Immune Response

2019 ◽  
Vol 88 (2) ◽  
Author(s):  
Jing Liu ◽  
Guilian Yang ◽  
Haibin Huang ◽  
Chunwei Shi ◽  
Xing Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Lactobacillus Plantarum ◽  
Influenza Virus Infection ◽  
Cell Culture Supernatant ◽  
Single Chain ◽  
Ifn Γ

ABSTRACT Influenza A virus (H1N1) is an acute, highly contagious respiratory virus. The use of lactic acid bacteria (LAB) to deliver mucosal vaccines against influenza virus infection is a research hot spot. In this study, two recombinant Lactobacillus plantarum strains expressing hemagglutinin (HA) alone or coexpressing aCD11c-HA to target HA protein to dendritic cells (DCs) by fusion to an anti-CD11c single-chain antibody (aCD11c) were constructed. The activation of bone marrow dendritic cells (BMDCs) by recombinant strains and the interaction of activated BMDCs and sorted CD4+ or CD8+ T cells were evaluated through flow cytometry in vitro, and cellular supernatants were assessed by using an enzyme-linked immunosorbent assay kit. The results demonstrated that, compared to the HA strain, the aCD11c-HA strain significantly increased the activation of BMDCs and increased the production of CD4+ gamma interferon-positive (IFN-γ+) T cells, CD8+ IFN-γ+ T cells, and IFN-γ in the cell culture supernatant in vitro. Consistent with these results, the aCD11c-HA strain clearly increased the activation and maturation of DCs, the HA-specific responses of CD4+ IFN-γ+ T cells, CD8+ IFN-γ+ T cells, and CD8+ CD107a+ T cells, and the proliferation of T cells in the spleen, finally increasing the levels of specific antibodies and neutralizing antibodies in mice. In addition, the protection of immunized mice was observed after viral infection, as evidenced by improved weight loss, survival, and lung pathology. The adoptive transfer of CD8+ T cells from the aCD11c-HA mice to NOD/Lt-SCID mice resulted in a certain level of protection after influenza virus infection, highlighting the efficacy of the aCD11c targeting strategy.

Obesity worsens the outcome of influenza virus infection associated with impaired type I interferon induction in mice

2019 ◽  
Vol 513 (2) ◽  
pp. 405-411 ◽  
Author(s):  
Ho Namkoong ◽  
Makoto Ishii ◽  
Hideki Fujii ◽  
Takahiro Asami ◽  
Kazuma Yagi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Type I Interferon ◽  
Influenza Virus Infection ◽  
Type I ◽  
Interferon Induction

scholarly journals Cytosolic DNA sensor-initiated innate immune responses in mouse ovarian granulosa cells

Reproduction ◽  
2017 ◽  
Vol 153 (6) ◽  
pp. 821-834 ◽  
Author(s):  
Keqin Yan ◽  
Dingqing Feng ◽  
Jing Liang ◽  
Qing Wang ◽  
Lin Deng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Granulosa Cells ◽  
Innate Immune ◽  
Type I Interferons ◽  
Endocrine Function ◽  
Type I ◽  
Dna Sensor ◽  
Innate Immune Responses ◽  
Oligoadenylate Synthetase ◽  
Ovarian Granulosa Cells

Viral infections of the ovary may perturb ovarian functions. However, the mechanisms underlying innate immune responses in the ovary are poorly understood. The present study demonstrates that cytosolic viral DNA sensor signaling initiates the innate immune response in mouse ovarian granulosa cells and affects endocrine function. The cytosolic DNA sensors p204 and cGAS and their common signaling adaptor stimulator of interferon (IFN) genes (STING) were constitutively expressed in granulosa cells. Transfection with VACV70, a synthetic vaccinia virus (VACV) DNA analog, induced the expression of type I interferons (IFNA/B) and major inflammatory cytokines (TNFA and IL6) through IRF3 and NF-κB activation respectively. Moreover, several IFN-inducible antiviral proteins, including 2′,5′-oligoadenylate synthetase, IFN-stimulating gene 15 and Mx GTPase 1, were also induced by VACV70 transfection. The innate immune responses in granulosa cells were significantly reduced by the transfection of specific small-interfering RNAs targeting p204, cGas or Sting. Notably, the VACV70-triggered innate immune responses affected steroidogenesis in vivo and in vitro. The data presented in this study describe the mechanism underlying ovarian immune responses to viral infection.

scholarly journals Plasmacytoid Dendritic Cells Are Dispensable during Primary Influenza Virus Infection

2009 ◽  
Vol 182 (2) ◽  
pp. 871-879 ◽  
Author(s):  
Amaya I. Wolf ◽  
Darya Buehler ◽  
Scott E. Hensley ◽  
Lois L. Cavanagh ◽  
E. John Wherry ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Plasmacytoid Dendritic Cells
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