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Borrelia burgdorferi induces a type I interferon response during early stages of disseminated infection in mice.

BACKGROUND: Lyme borrelia genotypes differ in their capacity to cause disseminated disease. Gene array analysis was employed to profile the host transcriptome induced by Borrelia burgdorferi strains with different capacities for causing disseminated disease in the blood of C3H/HeJ mice during early infection. RESULTS: B. burgdorferi B515, a clinical isolate that causes disseminated infection in mice, differentially regulated 236 transcripts (P < 0.05 by ANOVA, with fold change of at least 2). The 216 significantly induced transcripts included interferon (IFN)-responsive genes and genes involv

Twenty-five years of type I interferon-based treatment: a critical analysis of its therapeutic use.

The clinical exploitation of type I interferon (IFN) as an antiviral and antineoplastic agent is based on the properties originally attributed to this cytokine family, with schedules reflecting only their antiviral and antiproliferative activities. Nevertheless, type I IFN has emerged as a central activator of the innate immunity. As current schedules of treatment for chronic hepatitis C and for hematological and solid tumors, based on the continuous administration of recombinant type I IFN or pegylated formulations, disregard viral resistance, host genetic variants predicting treatment outcom

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… Expression of biomarkers of interferon type I in patients suffering from chronic diseases Clin Exp Immunol 147 2007 270 276 17223968 10.1111/j.1365-2249.2006.03280.x PMC1810469 85 Dill M.T. Makowska Z. Duong F.H. Merkofer F. Filipowicz M. Baumert T.F. …

STING-dependent recognition of cyclic di-AMP mediates type I interferon responses during Chlamydia trachomatis infection.

UNLABELLED: STING (stimulator of interferon [IFN] genes) initiates type I IFN responses in mammalian cells through the detection of microbial nucleic acids. The membrane-bound obligate intracellular bacterium Chlamydia trachomatis induces a STING-dependent type I IFN response in infected cells, yet the IFN-inducing ligand remains unknown. In this report, we provide evidence that Chlamydia synthesizes cyclic di-AMP (c-di-AMP), a nucleic acid metabolite not previously identified in Gram-negative bacteria, and that this metabolite is a prominent ligand for STING-mediated activation of IFN respons

Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection.

Streptococcus pyogenes is a Gram-positive human pathogen that is recognized by yet unknown pattern recognition receptors (PRRs). Engagement of these receptor molecules during infection with S. pyogenes, a largely extracellular bacterium with limited capacity for intracellular survival, causes innate immune cells to produce inflammatory mediators such as TNF, but also type I interferon (IFN). Here we show that signaling elicited by type I IFNs is required for successful defense of mice against lethal subcutaneous cellulitis caused by S. pyogenes. Type I IFN signaling was accompanied with reduce

Effect of type I interferon(s) on cell viability and apoptosis in primary human thyrocyte cultures.

BACKGROUND: Interferon (IFN) therapy may induce a generalized activation of the immune system, hence triggering or exacerbating autoimmune disease. Apoptosis contributes to the development of hypothyroidism in autoimmune thyroiditis. IFN can affect all phases of the cell cycle and may induce apoptosis in several cell lines from varied histologies. To date, no data exist on the possible effect of type I IFN(s) on FAS/FASL system and cell apoptosis of human thyroid follicles. Therefore, we evaluated the effect of both IFN-alpha and -beta on apoptosis in primary human thyrocyte cultures and the p

Conserved herpesviral kinase promotes viral persistence by inhibiting the IRF-3-mediated type I interferon response.

A conserved herpesviral kinase, designated ORF36 in murine gamma-herpesvirus 68 (MHV-68), plays multiple vital roles in the viral life cycle. Here, we show by screening mutant viruses that ORF36 counteracts the antiviral type I interferon (IFN) response. ORF36 specifically binds to the activated form of interferon regulatory factor 3 (IRF-3) in the nucleus, inhibiting IRF-3 interaction with the cotranscriptional activator CBP and thereby suppressing the recruitment of RNA polymerase II to the interferon beta promoter. The anti-IFN function of ORF36 is conserved among herpesvirus subfamilies, a

Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease.

BACKGROUND & AIMS: T-helper (Th)1 cells play a central role in the pathogenesis of tissue damage in Crohn's disease (CD). Interleukin (IL)-12/STAT4 signaling promotes Th1 cell commitment in CD, but other cytokines are needed to maintain activated Th1 cells in the mucosa. In this study, we examined the expression and role of IL-21, a T-cell-derived cytokine of the IL-2 family; in tissues and cells isolated from patients with inflammatory bowel disease. METHODS: IL-21 was examined by Western blotting in whole mucosa and lamina propria mononuclear cells (LPMCs) from patients with CD, ulcerative

Viruses evade the immune system through type I interferon-mediated STAT2-dependent, but STAT1-independent, signaling.

Understanding, treating, and preventing diseases caused by immunosuppression and/or persistent infections remain both a major challenge in biomedical research and an important health goal. For a virus or any infectious agent to persist, it must utilize strategies to suppress or evade the host's immune response. Here, we report that two dissimilar viruses employ a common maneuver to cause a profound immunosuppression. Measles virus (MV) and lymphocytic choriomeningitis virus (LCMV) interfere with dendritic cell (DC) development and expansion in vivo and in vitro. The underlying mechanism for th

HIV-1 gp41 and type I interferon: sequence homology and biological as well as clinical implications.

HIV-1 gp41-like human type I interferon (IFN) could inhibit lymphocyte proliferation and up-modulate MHC class I and II and ICAM-1 molecule expression. Sequence comparison indicates that a similar epitope RILAV-YLKD exists between N-domain of gp41 and two regions in IFN-alpha(aa29-35 and 113-129), IFN-beta (aa31-37 and 125-138) and IFN-omega (aa29-35 and 123-136), which was shown to form IFN-alpha/beta-receptor binding site. Weak sequence similarity was also found to exist in both regions on gp41 and type I IFN of murine and bovine. Experimental studies indicated that a common immunological ep

Type I Interferon Signature is Associated With Lung Disease, Drug-Associated Immune Reactions, and Genetic Variation in Interferon-Linked Pathways in Still Disease.

OBJECTIVE: To evaluate the relationship across type I interferon (IFN-I)-stimulated gene (ISG) expression, Still disease, and the development of lung disease (LD) and drug-associated immune reactions (DAIR) to interleukin-1 (IL-1) and/or IL-6 inhibitors. METHODS: Whole blood ISG expression was quantified by NanoString array. ISG-28 scores were calculated in consecutive patients with Still or Still-like disease. Exome sequencing with family-based variant prioritization identified candidate genes harboring rare candidate causative variants. Lists of candidate genes were subjected to functional

Feline Herpesvirus 1 US3 Blocks the Type I Interferon Signal Pathway by Targeting Interferon Regulatory Factor 3 Dimerization in a Kinase-Independent Manner.

As a prevalent agent in cats, feline herpesvirus 1 (FHV-1) infection contributes to feline respiratory disease and acute and chronic conjunctivitis. FHV-1 can successfully evade the host innate immune response and persist for the lifetime of the cat. Several mechanisms of immune evasion by human herpesviruses have been elucidated, but the mechanism of immune evasion by FHV-1 remains unknown. In this study, we screened for FHV-1 open reading frames (ORFs) responsible for inhibiting the type I interferon (IFN) pathway with an IFN-β promoter reporter and analysis of IFN-β mRNA levels in HEK 293T

Local synthesis of interferon-alpha in lupus nephritis is associated with type I interferons signature and LMP7 induction in renal tubular epithelial cells.

INTRODUCTION: Type I interferons are pivotal in the activation of autoimmune response in systemic lupus erythematous. However, the pathogenic role of interferon-alpha in patients affected by lupus nephritis remains uncertain. The aim of our study was to investigate the presence of a specific interferon signature in lupus nephritis and the effects of interferon-alpha at renal level. METHODS: We performed immunohistochemical analysis for MXA-protein and in situ hybridization to detect interferon-alpha signature and production in human lupus nephritis. Through microarray studies, we analyzed the

Sustained type I interferon activity and N-antigenemia form a vicious cycle during severe COVID-19.

BACKGROUND: Although antigenemia is associated with poor outcomes in respiratory viral infections, the underlying mechanisms driving viral bloodstream dissemination remain not fully understood. Herein, we aimed to characterise SARS-CoV-2 nucleocapsid (N)-antigenemia kinetics in patients with severe COVID-19. We also sought to identify host and viral determinants associated with viral dissemination through a multiparametric integrated analysis and assess the associated risk of death. METHODS: This observational study included hospitalised patients with severe COVID-19 across three independent

Hippo kinase NDR1 crosstalks with GSK3 and positively regulates type I interferon-mediated antiviral innate immunity.

Type I interferons (IFN-Is) are central mediators of antiviral innate immunity, yet the molecular pathways that fine-tune their rapid induction remain incompletely defined. Here, we identified the Hippo pathway kinase NDR1 as a key positive regulator of IFN-β-mediated antiviral responses. NDR1 forms a constitutive complex with GSK3 and selectively blocks its interaction with Akt, thereby preventing Akt-dependent inhibitory phosphorylation of GSK3 at Ser21/9 and maintaining GSK3 activity. Sustained GSK3 function enables efficient STAT1 activation, a central event required for both the initiatio

SIGLEC-1 expression on monocytes as a diagnostic biomarker in pediatric type I interferon-mediated diseases.

BACKGROUND: Type I interferon-mediated diseases present diagnostic challenges due to heterogeneous clinical manifestations and limitations of current molecular diagnostics, such as the type I interferon score (IS). OBJECTIVES: We sought to evaluate SIGLEC-1 expression on monocytes as a practical biomarker for type I interferon activation. METHODS: We conducted a combined retrospective (n = 47) and prospective (n = 62) study of patients with suspected interferon-mediated diseases. SIGLEC-1 expression was quantified by flow cytometry as mean fluorescence intensity (MFI) and percentage of SIGLE

Lycorine from Lycoris radiata attenuates IBV-induced pathogenicity by boosting MDA5-dependent type I interferon response.

ETHNOPHARMACOLOGICAL RELEVANCE: The bulb of Lycoris radiata (L'Hér.) Herb. (Amaryllidaceae) has been widely utilized in Traditional Chinese Medicine (TCM) for its properties of "clearing heat and relieving toxicity" (Qing Re Jie Du) and "eliminating phlegm" (Qu Tan), and is frequently prescribed for throat inflammation, abscesses, and ulcers. Although lycorine is known as the main active alkaloid, its specific activity against the avian respiratory coronavirus, infectious bronchitis virus (IBV), remains unexplored, despite the plant's long-standing use for respiratory ailments. AIM OF THE STU

Nipah virus Malaysia and Bangladesh strain-induced pathogenesis in mice lacking type I interferon receptor signaling.

Nipah virus (NiV) is a zoonotic highly pathogenic Paramyxovirus inducing lethal outbreaks of encephalitis and Acute Respiratory Distress Syndrome (ARDS) with an average case-fatality rate of 75%. Two viral strains, NiV-Malaysia (NiV-Mal) and NiV-Bangladesh (NiV-Ban), associated to distinct route of transmission, symptoms and lethality have been described. Due to the permanent threat of these emerging infections and the lack of approved therapeutics, it is crucial to improve our understanding regarding NiV-associated pathogenesis. Mice represent a small and accessible animal model, provided wit

IFI44 Functions as a Positive Regulator of Type I Interferon Signaling to Restrict Zika Virus Infection.

Zika virus (ZIKV) infection is known to cause microcephaly in newborns, and its outbreaks have previously emerged as a global public health crisis. The lack of a preventive vaccine or specific antiviral drugs underscores the urgency of investigating the detailed mechanisms of pathogenesis. We identified that interferon-induced protein 44 (IFI44) is significantly upregulated following ZIKV infection, but its role in ZIKV pathogenesis remains unclear. Using A549 and 2FTGH cells, we established ZIKV-infected cell models and employed quantitative real-time PCR and Western blotting to demonstrate t

BXSB.Yaa: A Translational Model of Toll-Like Receptor 7-Type I Interferon-Driven Systemic Lupus Erythematosus.

Despite recent approvals of belimumab and anifrolumab, durable, steroid-sparing remission in systemic lupus erythematosus (SLE) remains uncommon, underscoring ongoing therapeutic needs. The BXSB.Yaa mouse model, harbouring Y-linked Tlr7 duplication on a polygenic susceptibility background, has been instrumental in elucidating the TLR7-type I interferon (IFN1) axis central to SLE. This review positions BXSB.Yaa as a comparative model system and advances a mechanism-aligned framework that maps murine models to human SLE endotypes (e.g., IFN1-high vs. IFN-γ-dominant; germinal center- vs. extrafol

Köhlmeier-Degos disease is an interferonopathy characterized by type I and II interferon-driven inflammatory vasculopathy.

Köhlmeier-Degos disease (Degos disease [DD]) is a rare vasculopathy with characteristic skin lesions and life-threatening gastrointestinal and cerebrovascular involvement. Although DD is often viewed as a thrombo-obliterative disorder, its immunopathology remains poorly defined. Here, single-cell RNA and T cell receptor sequencing of skin, blood, and cerebrospinal fluid from DD patients reveal pervasive type I and type II interferon activation, with an interferon-γ-biased program compared with systemic lupus erythematosus. Cytotoxic CD8A+ T cells show interferon-responsive activation and restr