Innate immune responses and type 1 diabetes: A role for a long non-coding RNA?

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
MP Ashton ◽  
I Tan ◽  
L Mackin ◽  
C Elso ◽  
E Chu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes

2012 ◽  
Vol 210 (1) ◽  
pp. 191-203 ◽  
Author(s):  
Qibin Zhang ◽  
Thomas L. Fillmore ◽  
Athena A. Schepmoes ◽  
Therese R.W. Clauss ◽  
Marina A. Gritsenko ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Responses ◽  
Innate Immune ◽  
Healthy Controls ◽  
Innate Immune Responses ◽  
C1 Inhibitor ◽  
Serum Samples ◽  
Healthy Control

Using global liquid chromatography-mass spectrometry (LC-MS)–based proteomics analyses, we identified 24 serum proteins that were significantly variant between those with type 1 diabetes (T1D) and healthy controls. Functionally, these proteins represent innate immune responses, the activation cascade of complement, inflammatory responses, and blood coagulation. Targeted verification analyses were performed on 52 surrogate peptides representing these proteins, with serum samples from an antibody standardization program cohort of 100 healthy control and 50 type 1 diabetic subjects. 16 peptides were verified as having very good discriminating power, with areas under the receiver operating characteristic curve ≥0.8. Further validation with blinded serum samples from an independent cohort (10 healthy control and 10 type 1 diabetics) demonstrated that peptides from platelet basic protein and C1 inhibitor achieved both 100% sensitivity and 100% specificity for classification of samples. The disease specificity of these proteins was assessed using sera from 50 age-matched type 2 diabetic individuals, and a subset of proteins, C1 inhibitor in particular, were exceptionally good discriminators between these two forms of diabetes. The panel of biomarkers distinguishing those with T1D from healthy controls and those with type 2 diabetes suggests that dysregulated innate immune responses may be associated with the development of this disorder.

scholarly journals The role of type 1 interferons in Gram-negative bacteria-induced coagulation

Blood ◽  
2020 ◽  
Author(s):  
Xinyu Yang ◽  
Xiaoye Cheng ◽  
Yiting Tang ◽  
Xianhui Qiu ◽  
Zhongtai Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Bacterial Infection ◽  
Innate Immune ◽  
Coagulation Cascade ◽  
Outer Cell ◽  
Gram Negative Bacteria ◽  
Innate Immune Responses ◽  
Gram Negative ◽  
Type 1 Interferons

Bacterial infection not only stimulates innate immune responses but also activates the coagulation cascades. Over-activation of the coagulation system in bacterial sepsis leads to disseminated intravascular coagulation (DIC), a life-threatening condition. However, the mechanisms by which bacterial infection activates the coagulation cascade are not fully understood. Here we show that type 1 interferons (IFNs), widely expressed family of cytokines that orchestrate innate antiviral and antibacterial immunity, mediate bacterial infection-induced DIC through amplifying the release of high mobility box group box 1 (HMGB1) into the blood stream. Inhibition of the expression of type 1 IFNs, disruption of their receptor IFN-α/βR or downstream effector (e.g., HMGB1) uniformly decreased Gram-negative bacteria-induced DIC. Mechanistically, extracellular HMGB1 markedly increased the pro-coagulant activity of tissue factor (TF) by promoting the externalization of phosphatidylserine (PS) to the outer cell surface, where PS assembles a complex of cofactor-proteases of the coagulation cascades. These findings not only provide novel insights into the link between innate immune responses and coagulation, but also open a new avenue for developing novel therapeutic strategies to prevent DIC in sepsis.

scholarly journals Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Chu ◽  
Chenhui Li ◽  
Yongxing Li ◽  
Qiuya Yu ◽  
Huansha Yu ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Therapeutic Benefit ◽  
Perilla Frutescens ◽  
Innate Immune ◽  
Interferon Response ◽  
Innate Immune Responses ◽  
Simplex Virus

Cyclic GMP-AMP synthase (cGAS), serving as a primary sensor of intracellular DNA, is essential to initiate anti-microbial innate immunity. Inappropriate activation of cGAS by self-DNA promotes severe autoinflammatory diseases such as Aicardi–Goutières syndrome (AGS); thus, inhibition of cGAS may provide therapeutic benefit in anti-autoimmunity. Here we report that perillaldehyde (PAH), a natural monoterpenoid compound derived from Perilla frutescens, suppresses cytosolic-DNA-induced innate immune responses by inhibiting cGAS activity. Mice treated with PAH are more susceptible to herpes simplex virus type 1 (HSV-1) infection. Moreover, administration with PAH markedly ameliorates self-DNA-induced autoinflammatory responses in a mouse model of AGS. Collectively, our study reveals that PAH can effectively inhibit cGAS-STING signaling and could be developed toward the treatment of cGAS-mediated autoimmune diseases.

scholarly journals miR-23a/b suppress cGAS-mediated innate and autoimmunity

2021 ◽  
Author(s):  
Qiuya Yu ◽  
Lei Chu ◽  
Yongxing Li ◽  
Quanyi Wang ◽  
Juanjuan Zhu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Autoimmune Diseases ◽  
Regulatory Mechanism ◽  
Disease Model ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Simplex Virus ◽  
Increased Susceptibility ◽  
Hsv 1

AbstractCyclic GMP-AMP synthase (cGAS), a key sensor of intracellular DNA, is essential for eliciting innate immunity against infection, whereas aberrant activation of cGAS by endogenous DNA promotes severe autoimmune diseases. However, it is largely unknown how cGAS expression is regulated during pathogen infection and autoimmunity. Here, we report that during herpes simplex virus type 1 (HSV-1) infection, two microRNAs (miR-23a and miR-23b) whose levels significantly decrease due to their interaction with the lncRNA Oasl2-209 directly regulate the expression of cGAS. Overexpression of miR-23a/b markedly dampens cytosolic DNA-induced innate immune responses, whereas inhibition of miR-23a/b enhances these responses. Mice treated with miR-23a/b agomirs exhibit increased susceptibility to HSV-1 infection. Moreover, cGAS is significantly upregulated in the Trex1−/− mouse autoimmune disease model. Administration of miR-23a/b blunts self DNA-induced autoinflammatory responses in Trex1−/− mice. Collectively, our study not only reveals a novel regulatory mechanism of cGAS expression by miRNAs but also identifies a potential therapy for cGAS-related autoimmune diseases.

Pattern Recognition Receptor-initiated Innate Immune Responses in mouse Prostatic Epithelial Cells

2021 ◽  
Author(s):  
Xiaoqin Yu ◽  
Ran Chen ◽  
Fei Wang ◽  
Weihua Liu ◽  
Wenjing Zhang ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Pattern Recognition Receptor ◽  
Innate Immune ◽  
Poly I:C ◽  
Innate Immune Responses ◽  
Local Inflammation ◽  
Recognition Receptor

Abstract Three major pathogenic states of the prostate, including benign prostatic hyperplasia, prostate cancer, and prostatitis, are related to the local inflammation. However, the mechanisms underlying the initiation of prostate inflammation remain largely unknown. Given that the innate immune responses of the tissue-specific cells to microbial infection or auto-antigens contribute to local inflammation, this study focused on pattern recognition receptor (PRR)-initiated innate immune responses in mouse prostatic epithelial cells (PECs). Primary mouse PECs abundantly expressed Toll-like receptor 3 (TLR3), TLR4, TLR5, melanoma differentiation-associated protein 5 (MDA5) and p204. These PRRs can be activated by their respective ligands: lipopolysaccharide (LPS) and flagellin of Gram-negative bacteria for TLR4 and TLR5, polyinosinic-polycytidylic acid (poly(I:C)) for TLR3 and MDA5, and herpes simplex virus DNA analog (HSV60) for p204. LPS and flagellin predominantly induced the expression of inflammatory cytokines, including TNFA, IL6, MCP1, and CXCL10. Poly(I:C) and HSV60 predominantly induced the expression of type 1 interferons (IFNA and IFNB) and antiviral proteins: Mx GTPase 1, 2′,5′-oligoadenylate synthetase 1, and IFN-stimulated gene 15. The replication of mumps virus in PECs was inhibited by type 1 IFN signaling. These findings provide insights into the mechanisms underlying innate immune response in the prostate.

scholarly journals Innate immune responses of domestic pigeons to the infection of pigeon paramyxovirus type 1 virus

2020 ◽  
Author(s):  
Fangfang Wang ◽  
Mengying Gao ◽  
Zongxi Han ◽  
Yutong Hou ◽  
Lili Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Domestic Pigeons ◽  
Pigeon Paramyxovirus Type 1

scholarly journals PRINS Non-Coding RNA Regulates Nucleic Acid-Induced Innate Immune Responses of Human Keratinocytes

2017 ◽  
Vol 8 ◽  
Author(s):  
Judit Danis ◽  
Anikó Göblös ◽  
Zsuzsanna Bata-Csörgő ◽  
Lajos Kemény ◽  
Márta Széll
Keyword(s):  
Nucleic Acid ◽  
Immune Responses ◽  
Human Keratinocytes ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Non Coding Rna

scholarly journals CD8 T Cells in Innate Immune Responses: Using STAT4-Dependent but Antigen-Independent Pathways to Gamma Interferon during Viral Infection

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Jenny E. Suarez-Ramirez ◽  
Margarite L. Tarrio ◽  
Kwangsin Kim ◽  
Delia A. Demers ◽  
Christine A. Biron
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Gamma Interferon ◽  
Innate Immune ◽  
Interleukin 12 ◽  
Innate Immune Responses ◽  
Ifn Γ

ABSTRACT The cytokine gamma interferon (IFN-γ), with antimicrobial and immunoregulatory functions, can be produced by T cells following stimulation through their T cell receptors (TCRs) for antigen. The innate cytokines type 1 IFNs and interleukin-12 (IL-12) can also stimulate IFN-γ production by natural killer (NK) but not naive T cells. High basal expression of signal transducer and activator of transcription 4 (STAT4), used by type 1 IFN and IL-12 to induce IFN-γ as well as CD25, contributes to the NK cell responses. During acute viral infections, antigen-specific CD8 T cells are stimulated to express elevated STAT4 and respond to the innate factors with IFN-γ production. Little is known about the requirements for cytokine compared to TCR stimulation. Primary infections of mice with lymphocytic choriomeningitis virus (LCMV) demonstrated that although the elicited antigen-specific CD8 T cells acquired STAT4-dependent innate cytokine responsiveness for IFN-γ and CD25 induction ex vivo, TCR stimulation induced these through STAT4-independent pathways. During secondary infections, LCMV-immune CD8 T cells had STAT4-dependent IFN-γ expression at times of innate cytokine induction but subsequently expanded through STAT4-independent pathways. At times of innate cytokine responses during infection with the antigen-distinct murine cytomegalovirus virus (MCMV), NK and LCMV-immune CD8 T cells both had activation of pSTAT4 and IFN-γ. The T cell IFN-γ response was STAT4 and IL-12 dependent, but antigen-dependent expansion was absent. By dissecting requirements for STAT4 and antigen, this work provides novel insights into the endogenous regulation of cytokine and proliferative responses and demonstrates conditioning of innate immunity by experience. IMPORTANCE Understanding the regulation and function of adaptive immunity is key to the development of new and improved vaccines. Its CD8 T cells are activated through antigen-specific receptors to contribute to long-lasting immunity after natural infections or purposeful immunization. The antigen-receptor pathway of stimulation can lead to production of gamma interferon (IFN-γ), a cytokine having both direct antimicrobial and immunoregulatory functions. Natural killer cells can also produce IFN-γ in response to the innate cytokines type 1 IFNs and/or interleukin-12. This work demonstrates that CD8 T cells acquire parallel responsiveness to innate cytokine signaling for IFN-γ expression during their selection and development and maintain this capability to participate in innate immune responses as long-lived memory cells. Thus, CD8 T cells are conditioned to play a role in innate immunity, and their presence under immune conditions has the potential to regulate resistance to either secondary challenges or primary infections with unrelated agents.

scholarly journals HIV-1 Is a Poor Inducer of Innate Immune Responses

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Oya Cingöz ◽  
Stephen P. Goff
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Cell Lines ◽  
Human Immunodeficiency Virus Type ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Sensors ◽  
Hiv 1

ABSTRACT Effective host immune responses against viral infection rely on the detection of the virus, activation of downstream signaling pathways, and the secretion of interferons (IFNs) and other cytokines. Many viruses can potently stimulate these responses, whereas the immune response against human immunodeficiency virus type 1 (HIV-1) remains relatively less well characterized. Here we show that HIV-1 infection with reporter viruses does not activate sensing pathways in cell lines and primary cells that are otherwise responsive to foreign nucleic acids. After entry into cells, reverse transcription and reporter expression occur without the virus ever being detected by cellular sensors or stimulating an interferon response. Using multiple methods, including the use of reporter cell lines for type I IFN and NF-κB pathway activation, quantifying mRNA levels for IFN-stimulated genes (ISGs), and assaying for markers of innate immune activation, we show that single-round pseudotyped HIV-1-based reporter viruses fail to induce innate immune responses. IMPORTANCE Human immunodeficiency virus type 1 (HIV-1) continues to be a major burden to human health worldwide. How infected cells recognize and respond to HIV-1 infection is important in order to better understand the biology of the virus and the cellular pathways activated upon infection and to identify potential targets that interfere with viral replication. In this study, we investigated innate immune responses of different cell types following infection with single-cycle (replication-defective) HIV-1 reporter virus. We report that infection with a commonly used HIV-1 strain (lacking the env, nef, and vpr genes) does not measurably activate cellular defense mechanisms and that the virus is able to avoid recognition by cellular sensors.

Oral Immune Activation by Disgust and Disease-Related Pictures

2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Negative Control ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Markers ◽  
Before And After ◽  
Secondary Analyses ◽  
Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

Sign in / Sign up

Export Citation Format

Share Document