27 research outputs found

    Respiratory syncytial virus glycoprotein G impedes CX3CR1-activation by CX3CL1 and monocyte function

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    Abstract The soluble form of the Respiratory Syncytial Virus (RSV) G protein (sG) bears resemblance to the chemokine fractalkine (CX₃CL1). Both RSV sG and CX3CL1 possess a mucin-like domain and a CX3C motif, exist in membrane-associated and soluble forms, and bind to the CX₃CR1 receptor expressed on immune and epithelial cells. To explore the biological significance of RSV sG and CX₃CR1 interaction, we produced wild type (WT) and CX₃C motif-deficient (CX3CMut) RSV sG proteins and determined their effects on CX₃CR1 signaling in monocytic cells. Both CX3CMut- and WT RSV sG failed to activate CX₃CR1 signaling directly. However, WT sG competed with CX₃CL1 for CX₃CR1 binding and reduced CX3CL1-induced CX₃CR1-activation, monocyte migration, and adhesion. The CX₃C motif of sG was crucial for competitive blocking of CX3CL1-mediated activation, as CX₃CMut sG did not affect these CX₃CR1 functions significantly. Thus, blockade of CX₃CR1 signaling by sG may allow RSV to dampen host immune responses

    Host Responses to Respiratory Syncytial Virus Infection

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    Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected with RSV by the age of two, and reinfections are common throughout life. Since antigenic variation, which is frequently observed among other respiratory viruses such as SARS-CoV-2 or influenza viruses, can only be observed for RSV to a limited extent, reinfections may result from short-term or incomplete immunity. After decades of research, two RSV vaccines were approved to prevent lower respiratory tract infections in older adults. Recently, the FDA approved a vaccine for active vaccination of pregnant women to prevent severe RSV disease in infants during their first RSV season. This review focuses on the host response to RSV infections mediated by epithelial cells as the first physical barrier, followed by responses of the innate and adaptive immune systems. We address possible RSV-mediated immunomodulatory and pathogenic mechanisms during infections and discuss the current vaccine candidates and alternative treatment options

    Ons eten gemeten. Gezonde voeding en veilig voedsel in Nederland

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    Verkrijgbaar bij Bohn, Stafleu, Van LoghumEnglish translation: RIVM report 270555009Ons voedsel is veiliger dan ooit, maar Nederlanders eten te veel en verkeerd. Hierdoor wordt aanzienlijk gezondheidsverlies geleden en leven we gemiddeld twee jaar korter. Dat zijn enkele belangrijke conclusies uit het rapport "Ons eten gemeten". Dit rapport geeft voor de eerste keer in Nederland een totaaloverzicht van de beschikbare kennis op het gebied van de voedselconsumptie, de voedselveiligheid, en de gevolgen voor de gezondheid op lange termijn.VW

    Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation

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    SummaryLung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8+ sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4+ and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma

    Integrated Criteria Document Arsenicum

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    Bij dit rapport behoort een appendix onder hetzelfde nummer getiteld: "Integrated Criteria document Arsenicum: Effects" Auteurs: Hesse JM;<br>Janus JA;<br>Krajnc EI; Kroese ED<br>This report contains a systematic review of the most relevant data on the priority-substance-group arsenic for the purpose of environmental policy.DGM/SR / Haring BJ
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