Loss of mandibular lymph node integrity is associated with an increase in sensitivity to HSV-1 infection in CD118-deficient mice.
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The adoptive transfer of HSV-specific TCR transgenic CD8+ T cells into CD118−/− mice at the time of infection modestly reduced viral titers in the nervous system suggesting in addition to the generation of HSv-specific CD8 + T cells, other type I IFN-activated pathways are instrumental in controlling acute infection.Abstract:
Type I IFNs are potent antiviral cytokines that contribute to the development of the adaptive immune response. To determine the role of type I IFNs in this process in an infectious disease model, mice deficient in the type I IFN receptor (CD118(-/-)) were ocularly infected with HSV-1 and surveyed at times post infection in the nervous system and lymph node for virus and the host immune response. Virus titers were elevated in the trigeminal ganglia and brain stem with virus disseminating rapidly to the draining lymph node of CD118(-/-) mice. T cell and plasmacytoid dendritic cell infiltration into the brain stem was reduced in CD118(-/-) mice following infection, which correlated with a reduction in CXCL10 but not CXCL9 expression. In contrast, CXCL1 and CCL2 levels were up-regulated in the brainstem of CD118(-/-) mice associated with an increase in F4/80(+) macrophages. By day 5 post infection, there was a significant loss in T, NK, and plasmacytoid dendritic cell numbers in the draining lymph nodes associated with an increase in apoptotic/necrotic T cells and an appreciable lack of HSV-specific CD8(+) T cells. The adoptive transfer of HSV-specific TCR transgenic CD8(+) T cells into CD118(-/-) mice at the time of infection modestly reduced viral titers in the nervous system suggesting in addition to the generation of HSV-specific CD8(+) T cells, other type I IFN-activated pathways are instrumental in controlling acute infection.read more
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Herpes simplex type I (HSV-1) infection of the nervous system: is an immune response a good thing?
TL;DR: A greater understanding of the contribution of resident glial cells and infiltrating leukocytes within the CNS in response to HSV-1 invasion is necessary to identify candidate molecules as targets for therapeutic intervention to reduce unwarranted inflammation coinciding with the maintenance of the anti-viral state.
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Resistance to HSV-1 Infection in the Epithelium Resides with the Novel Innate Sensor, IFI-16
TL;DR: It is reported that TLR signaling is expendable in herpes simplex virus (HSV)-1 containment as depicted by plaque assays of knockout mice resembling wild-type controls, and an IRF-3-dependent, IRF7- and TLR-independent innate sensor responsible for HSV containment at the site of acute infection is identified.
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Neuroinvasion and Inflammation in Viral Central Nervous System Infections
TL;DR: This review illustrates examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed, and highlights the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections.
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IFN-α-driven CCL2 production recruits inflammatory monocytes to infection site in mice
TL;DR: CCL2 expression driven by IFI-16 recognition of HSV-1 facilitates the recruitment of inflammatory monocytes into the cornea proper to control viral replication.
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Microglia and a Functional Type I IFN Pathway Are Required To Counter HSV-1–Driven Brain Lateral Ventricle Enlargement and Encephalitis
Christopher D. Conrady,Min Zheng,Nico van Rooijen,Douglas A. Drevets,Derek J. Royer,Anthony M. Alleman,Daniel J.J. Carr +6 more
TL;DR: Using magnetic resonance imaging and type I IFN receptor–deficient mouse chimeras, it is demonstrated HSV-1 gains access to the murine brain stem and subsequently brain ependymal cells, leading to enlargement of the cerebral lateral ventricle and infection of the brain parenchyma in mice.
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