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Contribution of local Salmonella infection to autoreactivity: divergent roles of type I interferons in colonization and autoantibody production.

UNLABELLED: Salmonella biofilm-associated amyloid protein curli is a potent inducer of systemic inflammation and autoimmunity, promoting anti-double-stranded DNA (dsDNA) autoantibodies and pro-inflammatory cytokines, including type I interferons (IFNs). Although type I IFNs are key drivers of autoantibody production in systemic lupus erythematosus (SLE), their role in bacterial biofilm-induced autoimmunity remains unclear. To address this, we utilized type I IFN receptor-deficient (Ifnar-/-) mice. Repeated curli administration induced anti-dsDNA autoantibodies independently of IFNAR signaling.

Dengue virus induces interferon-β by activating RNA sensing pathways in megakaryocytes.

Activation of innate receptors in megakaryocytes (MKs) may affect the ability to produce functional platelets. Low platelet count is one of the clinical manifestations of dengue virus (DENV) infection. In MKs, the effect of innate receptors during DENV-infection is not well studied. Here we used MEG-01 cells to investigate DENV serotype 2 induced innate receptors in these cells. DENV RNA was estimated by qRT-PCR in the culture supernatant. The expression of innate receptors was determined by western blot and qPCR. DENV infection led to increased expression of RIG-I at 24 hrs post-infection (hp

New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies.

Chronic hepatitis D (CHD), a global health problem, manifests as the most severe form of viral hepatitis. The causative agent, HDV, is the smallest known human virus; it replicates its circular single-stranded RNA genome in the nucleus of hepatocytes. HDV requires HBV-encoded envelope proteins for dissemination and de novo cell entry. However, HDV can also spread through cell division. Following entry into hepatocytes, replicative intermediates of HDV RNA are sensed by the pattern recognition receptor MDA5 (melanoma differentiation antigen 5) resulting in interferon (IFN)-β/λ induction. This I

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

Increasing evidence indicates that obesity is a risk factor for increased severity of influenza virus infection. However, its precise immunological mechanism is not fully understood. To investigate this, diet-induced obese (DIO) mice were established by feeding C57BL/6 male mice a high-fat diet for 16 weeks. DIO and lean control mice were infected intranasally with 3000 pfu of influenza A virus (IAV) (PR8/H1N1). Interestingly, we found adipose tissue located along the bronchus in naïve DIO mice. In addition, the Nos2 level was significantly higher and Arg1 level was significantly lower in lung

Type I interferon induces CXCL13 to support ectopic germinal center formation.

Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection-induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that res

Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice.

During RBC transfusion, production of alloantibodies against RBC non-ABO Ags can cause hemolytic transfusion reactions and limit availability of compatible blood products, resulting in anemia-associated morbidity and mortality. Multiple studies have established that certain inflammatory disorders and inflammatory stimuli promote alloimmune responses to RBC Ags. However, the molecular mechanisms underlying these findings are poorly understood. Type I IFNs (IFN-α/β) are induced in inflammatory conditions associated with increased alloimmunization. By developing a new transgenic murine model, we

Interferon at the crossroads of allergy and viral infections.

IFN-α/β was first described as a potent inhibitor of viral replication, but it is now appreciated that IFN signaling plays a pleiotropic role in regulating peripheral T cell functions. Recently, IFN-α/β was shown to block human Th2 development by suppressing the transcription factor GATA3. This effect is consistent with the role for IFN-α/β in suppressing allergic inflammatory processes by blocking granulocyte activation and IL-4-mediated B cell isotype switching to IgE. With the consideration of recent studies demonstrating a defect in IFN-α/β secretion in DCs and epithelial cells from indivi

Type I interferon reaction to viral infection in interferon-competent, immortalized cell lines from the African fruit bat Eidolon helvum.

Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to app

Childhood type 1 diabetes mellitus and risk factor of interactions between dietary cow's milk intake and HLA-DR3/DR4 genotype.

Short-term breastfeeding and early exposure to dairy products into infant diets, may be critical factors for development of type 1 diabetes. In this study, we investigate whether cow's milk proteins are risk factors for type 1 diabetes in genetically susceptible individuals (HLA DR3/DR4) by using statistical analysis and in silico approach. In order to verify the potential risk of the early introduction of cow's milk, we conducted this study to validate the veracity of this hypothesis in our population. We included 121 subjects, 55 type 1 diabetics and 74 controls from the region of Tlemcen (A

The effect of interferon gamma on conventional fractionated radiation-induced damage and fibrosis in the pelvic tissue of rabbits.

We aim to investigate the effect of interferon gamma (IFN-γ) on conventional fractionated radiation-induced damage and fibrosis in ureter and colorectal mucosa. Fifty-two rabbits were randomly divided into three groups comprising a conventional radiation group, an IFN-γ group, and a control group. X-rays were used to irradiate the pelvic tissues of the rabbits in the IFN-γ and conventional radiation groups. Five days after radiation exposure, the rabbits in the IFN-γ group were administered 250,000 U/kg IFN-γ intramuscularly once a week for 5 weeks. The rabbits in the conventional radiation gr

Neuronally released sympathetic neurotransmitters stimulate splenic interferon-gamma secretion from T cells in early type II collagen-induced arthritis.

OBJECTIVE: The sympathetic nervous system confers a proinflammatory effect during the early phase of type II collagen-induced arthritis (CIA). These effects might be mediated by up-regulation of cytokines such as interferon-gamma (IFNgamma) or chemokines such as CXCL1 (cytokine-induced neutrophil chemoattractant, or KC). This study aimed to identify the role of sympathetic neurotransmitters in splenic secretion of IFNgamma and KC shortly after the onset of CIA. METHODS: At different time points during CIA, we determined the density of sympathetic nerve fibers in the spleens of mice. Spleens w

Inhibition of interferon-stimulated JAK-STAT signaling by a tick-borne flavivirus and identification of NS5 as an interferon antagonist.

The tick-borne encephalitis (TBE) complex of viruses, genus Flavivirus, can cause severe encephalitis, meningitis, and/or hemorrhagic fevers. Effective interferon (IFN) responses are critical to recovery from infection with flaviviruses, and the mosquito-borne flaviviruses can inhibit this response. However, little is known about interactions between IFN signaling and TBE viruses. Langat virus (LGTV), a member of the TBE complex of viruses, was found to be highly sensitive to the antiviral effects of IFN. However, LGTV infection inhibited IFN-induced expression of a reporter gene driven by eit

Detection of functionally altered hepatitis C virus-specific CD4 T cells in acute and chronic hepatitis C.

Chronic hepatitis C is characterized by a weak or absent hepatitis C virus (HCV)-specific CD4(+) T-cell response in terms of antigen-specific proliferation or interferon gamma (IFN-gamma) secretion. To clarify whether this is due to the absence or functional impairment of antigen-specific CD4(+) T cells we developed an assay that relies on the induced expression of the T-cell activation marker CD25 and is therefore independent from cytokine secretion or proliferation. In 10 of 20 patients with chronic hepatitis C, a significant number of antigen-specific activated CD4(+) T cells (mean 1.06%/pa

Selective loss of natural killer T cells by apoptosis following infection with lymphocytic choriomeningitis virus.

Natural killer T (NKT) cells, a unique subpopulation of T cells, coexpress markers also present on NK cells and recognize the major histocompatibility complex class I-like CD1d1 molecule. We studied the effect of an acute virus infection on NKT cells. Mice were infected with the nonhepatotropic Armstrong strain of lymphocytic choriomeningitis virus (LCMV), and at various times postinfection, mononuclear cells from the liver, peritoneum, and spleen were isolated. It was found that within 2 to 3 days, there was a selective loss of NKT cells from the liver with an apparent rapid recovery within 8

Impaired interleukin-12 production in multiple sclerosis patients.

Multiple Sclerosis (MS), a disease of the human central nervous system, is believed to be a T cell mediated autoimmune disorder with genetic and environmental influences. Interleukin-12 (IL-12), a proinflammatory cytokine produced primarily by antigen presenting cells is a potent inducer of interferon-gamma (IFN-gamma) and other Th1 cytokines that may play an important role in MS pathogenesis. We have investigated IL-12 production induced by the T cell independent pathway in untreated and IFN-beta treated MS patients, healthy individuals and other neurological disease (OND) patients in respons

Chronic ethanol consumption induces the production of tumor necrosis factor-alpha and related cytokines in liver and adipose tissue.

Increases in monocyte/macrophage production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), parallel the evolution of liver injury in rats and humans with alcoholic liver disease. However, the possibility that TNF-alpha expression may be induced in other cell populations before serious liver disease develops has not been evaluated. To clarify this issue, mRNAs and/or protein levels of TNF-alpha and cytokines [interleukin (IL)-6, IL-10, transforming growth factor-beta (TGF)-beta, IL-12, and interferon-gamma] that regulate its biological activity were measured in sera,

Growth factor and proto-oncogene expression in psoriasis.

The expression of several proto-oncogenes and growth factors was analyzed in normal skin and psoriatic lesions by RNA blot hybridization. Isolation of intact RNA from frozen biopsy samples required immediate exposure to denaturants during tissue homogenization. Lipocortin II and cyclophilin transcripts were used as internal controls. These transcripts were abundant and slightly but significantly elevated in psoriatic lesions. When results were normalized according to these reference transcripts, there was no increase in the expression of c-myc, c-Ha-ras, c-erbB (EGF receptor), c-jun, or transf

BCAM-AKT2 fusion protein promotes unfolded protein response driven oncogenic signaling in SKOV3 epithelial ovarian cancer cell line.

In view of the rapidly increasing evidence that gene fusion mutations are frequent drivers of cancer, a deeper understanding of the molecular and functional hallmarks of specific gene fusions in epithelial ovarian cancer (EOC) is essential. In this work we sought to identify the molecular signature of the BCAM-AKT2 fusion protein in ovarian cancer cell lines and to assess the biological impact of the novel fusion in these cells. Our in-vitro results show that the BCAM-AKT2 fusion protein is engaged in proliferative action within EOC cell lines. Furthermore, RNA-seq analysis shows that the effe

Тип I Interferoning Aughment Autoriability in Neuromielit Optica Spectrum.

Нейромиелитное расстройство спектра (NMOSD) — аутоиммунное заболевание, характеризующееся антиаквапорином 4 (AQP4) повреждениями астроцита и последующим обезвоживанием. Предшествующие попытки лечить NMOSD с помощью интерферон-беты (IFN-β), терапии для лечения различных склерозов, привели к ухудшению активности заболеваний с неизвестным механизмом. Здесь в миэлоидных клетках как в периферии, так и в центральной нервной системе выявляется активная активация сигнала CGAS-STING-IFN-I. Аномальная реакция IFN-I приводит к увеличению числа антигенных антиреактивных Т клеток AQP4. Недостаток стиля мож

Совпадение в аннотации оригинала
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease characterized by anti-aquaporin 4 (AQP4) antibody-mediated astrocyte damage and subsequent demyelination. Prior attempts to treat NMOSD with interferon-beta (IFN-β), a disease-modifying therapy for multiple sclerosis, resulted in worsening of disease activity, with an unknown mechanism. …

Спино-цебеллар Атаксия 31, представляющая собой демиелионирующую болезнь: отчет по делу.

Spinocerebellar ataxia (SCA) — группа унаследованных расстройств, охватывающих различные виды и презентации. Одним из его типов, SCA31, является редкая атаксия, имеющая широкий спектр презентаций. Поэтому его ошибочно диагностируют с другим неврологическим расстройством. Здесь мы описываем 52-летнюю женщину с прогрессивным дисбалансом и слабостью нижней части конечности, у которой первоначально был диагностирован множественный склероз (MS), основанный на перивентральных поражениях МРТ и цереброспиновой жидкости олигоклональных полос. Она получала интерферон-бета четыре года без улучшения. Посл

Совпадение в аннотации оригинала
Spinocerebellar ataxia (SCA) is a group of inherited disorders that encompasses different types and presentations. One of its types, SCA31, … s (MS) based on periventricular MRI lesions and cerebrospinal fluid oligoclonal bands. She received interferon-beta for four years without improvement. After mistreatment for years, she was reassessed and, due to a strong family history of similar ataxic symptoms, was prompted to undergo genetic testing, which confirmed SCA31. This case highlights the diagnostic …