Interferon modulates central nervous system function

Reyes-Vázquez, C.; Prieto-Gómez, B.; Dafny, Nachum

doi:10.1016/j.brainres.2011.09.061

Cited by 42 publications

(27 citation statements)

References 120 publications

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“…Poly(I:C) induces type I IFNs [32], IFN- β more so than IFN- α , in microglia [27]. Despite some anti-inflammatory effects in the CNS, for example, IFN- β reduces the expression of proinflammatory cytokines [33, 34] and inhibits the infiltration of T cells [35], it directly induces neuronal cell death [36] and as found for other cytokines, excessive levels or inappropriate activity of type I IFNs can cause toxicity and even death (neurodegeneration) [37, 38]. Thus, the function of IFN- β in the CNS is somewhat controversial.…”

Section: Introductionmentioning

confidence: 99%

Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-βand Nitric Oxide Production

Matsui

Motoki

Yoshida³

2013

Mediators of Inflammation

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Therapeutic hypothermia protects neurons after injury to the central nervous system (CNS). Microglia express toll-like receptors (TLRs) that play significant roles in the pathogenesis of sterile CNS injury. To elucidate the possible mechanisms involved in the neuroprotective effect of therapeutic hypothermia, we examined the effects of hypothermic culture on TLR3-activated microglial release of interferon (IFN)-β and nitric oxide (NO), which are known to be associated with neuronal cell death. When rat or mouse microglia were cultured under conditions of hypothermia (33°C) and normothermia (37°C) with a TLR3 agonist, polyinosinic-polycytidylic acid, the production of IFN-β and NO in TLR3-activated microglia at 48 h was decreased by hypothermia compared with that by normothermia. In addition, exposure to recombinant IFN-β and sodium nitroprusside, an NO donor, caused death of rat neuronal pheochromocytoma PC12 cells in a concentration-dependent manner after 24 h. Taken together, these results suggest that the attenuation of microglial production of IFN-β and NO by therapeutic hypothermia leads to the inhibition of neuronal cell death.

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Section: Introductionmentioning

confidence: 99%

Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-βand Nitric Oxide Production

Matsui

Motoki

Yoshida³

2013

Mediators of Inflammation

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“…IFNs (named according to their ability to interfere with viral proliferation) were discovered in 1957 by the British bacteriologist Alick Isaacs and the Swiss microbiologist Jean Lindenmann in Great Britain [7,8]. They are secreted by numerous cells like T lymphocytes, macrophages and natural killer cells, and play an important role in the first line of defense against viral infections [9].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Neuroimmunomodulatory Activity of Recombinant Human Interferon α

Mehta

Mukherjee

Balasubramanian

et al. 2014

Neuroimmunomodulation

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Objective: Recombinant human interferon (rhIFN)-α is a potent immunoregulator having a wide range of therapeutic applications. In the present study, rhIFN-α was evaluated for its neuroimmunomodulatory activity. Method: Dose-dependent gene expression of cytokines and chemokines in the brain of rhIFN-administered mice was studied using real-time SYBR green PCR. Results: Statistically significant increase in expression levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IFN-γ were observed. Conclusion: The findings indicate that rhIFN-α may be used at an optimized dose to cause appropriate neuromodulation of cytokine/chemokine secretion that can aid in the development of therapeutic approaches for many infectious diseases of the central nervous system for which therapies are lacking.

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“…Thus, it was of interest that HSV-1 passage from TG to skin seemed to avoid LysM ϩ cells, perhaps because most skin infection is epidermal (5). Excessive IFN-I evasion may have downsides: IFN-I contributes to the homeostasis of immune cells (53) and possibly also neurons (54), so a complete blockade might compromise persistence in these cell types. Such compromises forced on persistent viruses provide potential means of improving infection control.…”

Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus 1 Interaction with Myeloid CellsIn Vivo

Shivkumar

Lawler

Milho

et al. 2016

J Virol

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Herpes simplex virus 1 (HSV-1) enters mice via olfactory epithelial cells and then colonizes the trigeminal ganglia (TG). Most TG nerve endings are subepithelial, so this colonization implies subepithelial viral spread, where myeloid cells provide an important line of defense. The outcome of infection of myeloid cells by HSV-1 in vitro depends on their differentiation state; the outcome in vivo is unknown. Epithelial HSV-1 commonly infected myeloid cells, and Cre-Lox virus marking showed nose and lung infections passing through LysM-positive (LysM ؉ ) and CD11c ؉ cells. In contrast, subcapsular sinus macrophages (SSMs) exposed to lymph-borne HSV-1 were permissive only when type I interferon (IFN-I) signaling was blocked; normally, their infection was suppressed. Thus, the outcome of myeloid cell infection helped to determine the HSV-1 distribution: subepithelial myeloid cells provided a route of spread from the olfactory epithelium to TG neurons, while SSMs blocked systemic spread. IMPORTANCEHerpes simplex virus 1 (HSV-1) infects most people and can cause severe disease. This reflects its persistence in nerve cells that connect to the mouth, nose, eye, and face. Established infection seems impossible to clear. Therefore, we must understand how it starts. This is difficult in humans, but mice show HSV-1 entry via the nose and then spread to its preferred nerve cells. We show that this spread proceeds in part via myeloid cells, which normally function in host defense. Myeloid infection was productive in some settings but was efficiently suppressed by interferon in others. Therefore, interferon acting on myeloid cells can stop HSV-1 spread, and enhancing this defense offers a way to improve infection control.T he alpha-, beta-, and gammaherpesviruses establish broadly neuro-, myelo-, and lymphotropic persistent infections (1). Less is known about acute infection, as sporadic transmission and late clinical presentation make it difficult to analyze. Acutely adaptive immunity exerts little restraint on viral tropism, so common themes are likely. The difficulty in clearing established infections makes these themes important to understand. Genomic comparisons indicate that herpesvirus infections long predate human speciation (2). Therefore, related mammalian herpesviruses are likely to share mechanisms of host colonization, allowing those of experimentally tractable hosts to provide new insights. Murid herpesviruses have particular value in this regard, as their hosts provide the main in vivo experimental model of mammalian biology.Murid herpesvirus 4 (MuHV-4) (a gammaherpesvirus), murine cytomegalovirus (MCMV) (a betaherpesvirus), and herpes simplex virus 1 (HSV-1) (an alphaherpesvirus) all enter mice via olfactory neurons (3-5). MuHV-4 and MCMV spread from there to lymph nodes (LNs) (4, 6), while HSV-1 spreads to trigeminal ganglia (TG) (5). Nonetheless, each virus penetrates the epithelium and so will encounter subepithelial myeloid cells. While these cells normally provide an early defense against invading p...

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Interferon modulates central nervous system function

Cited by 42 publications

References 120 publications

Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-βand Nitric Oxide Production

Hypothermia Reduces Toll-Like Receptor 3-Activated Microglial Interferon-βand Nitric Oxide Production

Evaluation of Neuroimmunomodulatory Activity of Recombinant Human Interferon α

Herpes Simplex Virus 1 Interaction with Myeloid CellsIn Vivo

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