Suppression of IL-12p70 formation by IL-2 or following macrophage depletion causes T-cell autoreactivity leading to CNS demyelination in HSV-1-infected mice

Lee, Der-Horng; Zandian, Mandana; Kuo, Jane Z.; Mott, Kevin R.; Chen, Shuang; Arditi, Moshe; Ghiasi, Homayon

doi:10.1371/journal.ppat.1006401

Cited by 10 publications

(9 citation statements)

References 74 publications

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“…In addition, the levels of P-selectin and IL-12p70 were not significantly different among the GN-BSI, GP-BSI and fungal-BSI patients ( P > .05), despite that previous studies have occasionally reported that P-selectin and IL-12p70 play an important role in the regulating immune activation and participating in inflammatory response when infection occurs. [36,37] Similar investigations of these factors need to be performed in the future.…”

Section: Discussionmentioning

confidence: 99%

The clinical value of IL-3, IL-4, IL-12p70, IL17A, IFN-γ, MIP-1β, NLR, P-selectin, and TNF-α in differentiating bloodstream infections caused by gram-negative, gram-positive bacteria and fungi in hospitalized patients

Yuan

Wang

2019

Medicine

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Early differential diagnosis of bloodstream infections (BSIs) caused by different sources and species of bacteria in hospitalized patients is crucial for the timely targeted interventions including appropriate use of antibiotics. The aim of this study was to identify 9 biomarkers for the early differentiation of gram-negative-bloodstream infection (GN-BSI), gram-positive (GP)-BSI, and fungal-BSI.A prospective study was conducted for a total of 390 inpatients who underwent blood culture in the Chinese PLA General Hospital from September 2015 to March 2018. Patients with positive culture of a single pathogen were divided into GN-BSI, GP-BSI, and Fungal-BSI groups, and a culture-negative disease control group was also established. The serum levels of macrophage inflammatory protein 1β (MIP-1β), tumor necrosis factor α (TNF-α), interleukin (IL)-3, interferon (IFN)-γ, IL-17A, IL-4, IL-12p70, and P-selectin were detected and the NLR was calculated from routine blood test. Receiver-operating characteristic analysis was used to determine the efficacy of various indicators in the differential diagnosis of BSIs. Prediction and validation experiments on clinical patient samples (263 cases) were also performed.The level of IL-3 in the GP-BSI group was significantly higher than those in the other 3 groups. The level of IFN-γ in the fungal-BSI group was significantly higher than those in the other 3 groups. NLR, MIP-1β, TNF-α, IL-17A, and IL3 exhibited some efficacy when distinguishing between GN-BSI and GP-BSI and NLR had the largest area under curve (AUC) (0.728), followed by MIP-1β with an AUC of 0.679. IFN-γ and IL-3 exhibited some value in differential diagnosis between GN-BSI and Fungal-BSI. IL-3, MIP-1β, TNF-α, IFN-γ, NLR, IL-17A, and IL-4 exhibited some value in distinguishing fungal-BSI and GP-BSI, with IL-3 had the largest AUC (0.722), followed by MIP-1β with an AUC of 0.703.NLR and MIP-1β may be valuable in differentiating GN-BSI from GP-BSI in hospitalized patients. IFN-γ and IL-3 may be helpful in differential diagnosis GN-BSI and fungal-BSI. IL-3 and MIP-1β exhibited some diagnostic efficacy in distinguishing fungal-BSI and GP-BSI. Additionally, IL-3 with high serum level may be a marker for GP-BSI and IFN-γ with high serum level may be a valuable marker for the prediction of Fungal-BSI. The utility of these biomarkers to predict BSIs owing to different pathogens in hospitalized patients needs to be assessed in further studies.

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Section: Discussionmentioning

confidence: 99%

The clinical value of IL-3, IL-4, IL-12p70, IL17A, IFN-γ, MIP-1β, NLR, P-selectin, and TNF-α in differentiating bloodstream infections caused by gram-negative, gram-positive bacteria and fungi in hospitalized patients

Yuan

Wang

2019

Medicine

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“…They believe that it plays a crucial role in sustaining hypo-immune phenotype leading to chronic deteriorations. Another study showed that a suppression of IL-12p70, and not other members of IL-12 family, is linked to demyelination while an increase in IL-12p70 reversed the process (Lee et al, 2017 ). Interestingly, IL-12 family including IL-12p70 are important for the activation of IFN-γ supporting a strong link between the two in inflammation (Gee et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Treatment With Nilvadipine Mitigates Inflammatory Pathology and Improves Spatial Memory in Aged hTau Mice After Repetitive Mild TBI

Morin

Mouzon

Ferguson

et al. 2018

Front. Aging Neurosci.

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Mild traumatic brain injury (mTBI) is the most common form of brain trauma worldwide. The effects of mTBI are not well-studied within the elderly population, yet older adults constitute a significant portion of all mTBI patients. Few preclinical studies have focused on the effects of mTBI, or mTBI treatments, in the aged brain, and none have explored repetitive mTBI (r-mTBI). In this study, we have administered our well-characterized 5-injury model (5 r-mTBI) to hTau mice aged 24 months to explore the neurobehavioral and neuropathological outcomes, and the effects of treatment with the dihydropyridine, Nilvadipine. Our previous studies have shown that Nilvadipine inhibits spleen tyrosine kinase (Syk), is effective at reducing inflammation, tau hyperphosphorylation, and amyloid production, and it has recently been investigated in a European Phase III clinical trial for Alzheimer’s disease (AD). In our 24-month-old r-mTBI mice, we observed increased neuroinflammation and a trend toward impaired cognitive performance compared to sham controls. Treatment with Nilvadipine mitigated the TBI-induced inflammatory response in aged r-mTBI animals and significantly improved spatial memory. To our knowledge, this is the only preclinical study focusing on the treatment of r-mTBI in aged, and these results suggest a therapeutic potential of Nilvadipine for consequences of mTBI.

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“…Early studies with animal models showed latent TG infections and demyelinating lesions in mice intranasally infected with HSV-1 [ 107 ]. Later research also reported that mice infected with HSV-1 can develop lethal encephalitis or virus-induced CNS multifocal demyelinating lesions, with outcome affected by several factors, including the route of infection and mouse strain [ 108 , 109 , 110 , 111 , 112 ]. Demyelinating lesions have also been associated with HSV-1-induced facial nerve paralysis [ 113 ].…”

Section: Hsv-1 and Demyelinationmentioning

confidence: 99%

The Role of Herpes Simplex Virus Type 1 Infection in Demyelination of the Central Nervous System

Bello-Morales

Andreu

Löpez‐Guerrero

2020

IJMS

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Herpes simplex type 1 (HSV-1) is a neurotropic virus that infects the peripheral and central nervous systems. After primary infection in epithelial cells, HSV-1 spreads retrogradely to the peripheral nervous system (PNS), where it establishes a latent infection in the trigeminal ganglia (TG). The virus can reactivate from the latent state, traveling anterogradely along the axon and replicating in the local surrounding tissue. Occasionally, HSV-1 may spread trans-synaptically from the TG to the brainstem, from where it may disseminate to higher areas of the central nervous system (CNS). It is not completely understood how HSV-1 reaches the CNS, although the most accepted idea is retrograde transport through the trigeminal or olfactory tracts. Once in the CNS, HSV-1 may induce demyelination, either as a direct trigger or as a risk factor, modulating processes such as remyelination, regulation of endogenous retroviruses, or molecular mimicry. In this review, we describe the current knowledge about the involvement of HSV-1 in demyelination, describing the pathways used by this herpesvirus to spread throughout the CNS and discussing the data that suggest its implication in demyelinating processes.

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Suppression of IL-12p70 formation by IL-2 or following macrophage depletion causes T-cell autoreactivity leading to CNS demyelination in HSV-1-infected mice

Cited by 10 publications

References 74 publications

The clinical value of IL-3, IL-4, IL-12p70, IL17A, IFN-γ, MIP-1β, NLR, P-selectin, and TNF-α in differentiating bloodstream infections caused by gram-negative, gram-positive bacteria and fungi in hospitalized patients

The clinical value of IL-3, IL-4, IL-12p70, IL17A, IFN-γ, MIP-1β, NLR, P-selectin, and TNF-α in differentiating bloodstream infections caused by gram-negative, gram-positive bacteria and fungi in hospitalized patients

Treatment With Nilvadipine Mitigates Inflammatory Pathology and Improves Spatial Memory in Aged hTau Mice After Repetitive Mild TBI

The Role of Herpes Simplex Virus Type 1 Infection in Demyelination of the Central Nervous System

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