Loss of mandibular lymph node integrity is associated with an increase in sensitivity to HSV-1 infection in CD118-deficient mice.
TLDR
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
Citations
More filters
Journal ArticleDOI
IFN-λ Regulates Neutrophil Biology to Suppress Inflammation in Herpes Simplex Virus-1-Induced Corneal Immunopathology.
Ferrin Antony,Chetan Pundkar,Maninder Sandey,Anil Kumar Jaiswal,Amarjit Mishra,Ashok Kumar,Rudragouda Channappanavar,Amol Suryawanshi +7 more
TL;DR: In this article, the authors examined the therapeutic efficacy of exogenous topical rIFN-λ during SK progression and showed that early rifNλ treatment significantly reduced neutrophil and macrophage infiltration, and IL-6, IL-1β, and CXCL-1 production in the cornea.
Journal Article
The Herpes Simplex Virus Type 1 Latency Associated Transcript Inhibits Phenotypic and Functional Maturation of Dendritic Cells
Lbachir BenMohamed,Aziz Alami Chentoufi,Xavier Dervillez,Gargi Dasgupta,Chelsea Nguyen,Khaled K. Kabbara,Steven L. Wechsler,Anthony B. Nesburn +7 more
TL;DR: The results suggest a novel immune-evasion mechanism whereby the HSV-1 LAT increases the number of HSv-1 Ag-positive DCs in latently-infected TG, and interferes with DC phenotypic and functional maturation.
Journal ArticleDOI
Noncognate Signals Drive Enhanced Effector CD8+ T Cell Responses through an IFNAR1-Dependent Pathway after Infection with the Prototypic Vaccine, 0ΔNLS, against Herpes Simplex Virus 1
TL;DR: A side-by-side analysis of the primary infection characterizing differences of the host immune response in mice infected with 0ΔNLS versus the parental, GFP105 shows that local viral infection and replication are controlled more efficiently in mice exposed to 0Γ NLS versus GFP 105 but that the clearance of infectious virus is equivalent when the two groups are compared.
Journal ArticleDOI
Type I Interferon Signaling Is Critical During the Innate Immune Response to HSV-1 Retinal Infection
TL;DR: In this article , a reproducible mouse model of acute retinal necrosis (ARN) mimics human disease to better understand innate immunity within the retina during virus infection was created.
Journal ArticleDOI
Role of Innate Interferon Responses at the Ocular Surface in Herpes Simplex Virus-1-Induced Herpetic Stromal Keratitis
TL;DR: A review of the current understanding of HSV-1 recognition by PRRs and innate IFN-mediated antiviral immunity during infection of the cornea is presented in this article .
References
More filters
Journal ArticleDOI
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
Journal ArticleDOI
Interferon-inducible antiviral effectors
TL;DR: This Review discusses four main effector pathways of the IFN-mediated antiviral response: the Mx GTPase pathway, the 2′,5′-oligoadenylate-synthetase-directed ribonuclease L pathways, the protein kinase R pathway and the ISG15 ubiquitin-like pathway.
Journal ArticleDOI
Natural adjuvants: Endogenous activators of dendritic cells
TL;DR: It is reported here that, in the absence of any foreign substances, dendritic cells can be activated by endogenous signals received from cells that are stressed, virally infected or killed necrotically, but not by healthy cells or those dying apoptotically.
Journal ArticleDOI
Targeted Disruption of the Mouse Stat1 Gene Results in Compromised Innate Immunity to Viral Disease
TL;DR: Cell and tissues from Stat1(-1-1) mice were unresponsive to IFN, but remained responsive to all other cytokines tested, indicating that STAT1 appears to be specific for IFN pathways that are essential for viability in the face of otherwise innocuous pathogens.
Journal ArticleDOI
Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming.
Alfonso Martín-Fontecha,Lindy L. Thomsen,Sara Brett,Craig Gerard,Martin Lipp,Antonio Lanzavecchia,Federica Sallusto +6 more
TL;DR: It is shown in mice that natural killer (NK) cells are rapidly recruited in a CCR7-independent, CXCR3-dependent manner to lymph nodes on stimulation by the injection of mature DCs, and an induced pathway of NK cell migration in antigen-stimulated lymph nodes is identified.