Novel evidence of microglial immune response in impairment of Dengue infection of CNS

Bhatt, Rushil S.; Kothari, Sweta; Gohil, Devanshi; D’Souza, M.; Chowdhary, Abhay

doi:10.1016/j.imbio.2015.06.002

Cited by 37 publications

(40 citation statements)

References 23 publications

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“…It is widely accepted that microglia become activated following viral infection [39–43]. We observed that infected microglial cells follow the established activation profile after TC-83 infection (Supp.…”

Section: Resultsmentioning

confidence: 72%

Direct and indirect pro-inflammatory cytokine response resulting from TC-83 infection of glial cells

et al. 2018

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Venezuelan equine encephalitis virus (VEEV) is a neurotropic arbovirus that is highly infectious as an aerosol and can result in an encephalitic phenotype in infected individuals. VEEV infections are known to be associated with robust inflammation that eventually contributes to neurodegenerative phenotypes. In this study, we utilize the TC-83 strain of VEEV, which is known to induce the expression of IL-6, IL-8, and other pro-inflammatory cytokines. We had previously demonstrated that TC-83 infection resulted in changes in mitochondrial function, eventually resulting in mitophagy. In this manuscript, we provide data that links upstream mitochondrial dysfunction with downstream pro-inflammatory cytokine production in the context of microglia and astrocytoma cells. We also provide data on the role of bystander cells, which significantly contribute to the overall inflammatory load. Use of a mitochondrial-targeted antioxidant, mitoquinone mesylate, greatly reduced the inflammatory cytokine load and ameliorated bystander cell inflammatory responses more significantly than a broad-spectrum anti-inflammatory compound (BAY 11–7082). Our data suggest that the inflammatory mediators, especially IL-1β, may prime naïve cells to infection and lead to increased infection rates in microglial and astrocytoma cells. Cumulatively, our data suggest that the interplay between mitochondrial dysfunction and inflammatory events elicited in a neuronal microenvironment during a TC-83 infection may contribute to the spread of infection.

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Section: Resultsmentioning

confidence: 72%

Direct and indirect pro-inflammatory cytokine response resulting from TC-83 infection of glial cells

et al. 2018

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“…Total mRNA was extracted using the Trizol reagent and colonic epithelial cytokines evaluated by reverse transcription qPCR (RT-qPCR). The results were analyzed using the ΔΔCt method [64]. Fecal DNA was amplified with bacterial 16S rRNA-specific primers and the relative quantities of total bacteria and Bacteroides spp.…”

Section: Methodsmentioning

confidence: 99%

Isoliquiritigenin decreases the incidence of colitis-associated colorectal cancer by modulating the intestinal microbiota

Deng

et al. 2016

Oncotarget

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Imbalances in intestinal bacteria correlate with colitis-associated colorectal cancer (CAC). Traditional Chinese medicines have been used to adjust the gut microbiota, and isoliquiritigenin (ISL), a flavonoid extracted from licorice, has shown antitumor efficacy. In this study, the effects of ISL on CAC development and the gut microbiota were evaluated using an azoxymethane and dextran sulphate sodium (AOM/DSS)-induced mouse model of CAC (CACM). Histopathological analysis suggested that ISL reduced tumor incidence in vivo. Moreover, high-throughput sequencing and terminal restriction fragment length polymorphism (T-RFLP) studies of the bacterial 16S rRNA gene revealed that the structure of the gut microbial community shifted significantly following AOM/DSS treatment, and that effect was alleviated by treatment with high-dose ISL (150 mg/kg). Compared to the microbiota in the control mice (CK), the levels of Bacteroidetes decreased and the levels of Firmicutes increased during CAC development. ISL reversed the imbalance at the phylum level and altered the familial constituents of the gut microbiota. Specifically, the abundance of Helicobacteraceae increased after treatment with high-dose ISL, while the abundance of Lachnospiraceae and Rikenellaceae decreased. At the genus level, ISL reduced the abundance of opportunistic pathogens (Escherichia and Enterococcus), and increased the levels of probiotics, particularly butyrate-producing bacteria (Butyricicoccus, Clostridium, and Ruminococcus). Thus, ISL protects mice from AOM/DSS-induced CAC, and ISL and the gut microbiota may have synergistic anti-cancer effects.

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“…Activated microglia, which are resident macrophage-like immune cells in the brain, are widely present in neurological disorders including infection and may act as amplifiers for neuroinflammation 11 . Regarding the role of monocytes/macrophages as targets of DENV infection 12–15 , an in vitro study demonstrated that DENV infected and activated the microglial cell line BV2 by inducing the transcriptional activation of several inflammatory cytokines 16 . Based on the in vitro and in vivo results, microglia can be the targets of DENV in the brain; however, the effects of DENV on microglia require further investigation.…”

Section: Introductionmentioning

confidence: 99%

Dengue virus infection increases microglial cell migration

Jhan

Tsai

Chen

et al. 2017

Sci Rep

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Activated microglial cells are present in dengue virus (DENV)-infected brains; however, the possible effects of DENV on microglia remain unclear. Here, we demonstrated DENV caused infection, including viral entry, RNA replication, viral protein expression, and virus release, in the murine microglial cell line BV2. DENV infection caused an increase in the formation of the multipolar phenotype in vitro and in vivo without affecting cell growth and cytotoxicity. DENV infection considerably increased cell motility and disrupting either actin filaments or clathrin retarded such effect. Increase in cell migration was only occurred by DENV infection following a clathrin-regulated endocytosis of DENV entry. Ultraviolet-inactivated DENV did not affect cell migration, and pharmacologically blocking toll-like receptor (TLR) 3 and TLR3-related signaling pathways reduced the DENV-induced increase in cell migration. These results demonstrate an advanced effect of DENV infection on microglial migration via a mechanism involving viral entry, RNA release, and TLR3 signal activation.

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Novel evidence of microglial immune response in impairment of Dengue infection of CNS

Cited by 37 publications

References 23 publications

Direct and indirect pro-inflammatory cytokine response resulting from TC-83 infection of glial cells

Direct and indirect pro-inflammatory cytokine response resulting from TC-83 infection of glial cells

Isoliquiritigenin decreases the incidence of colitis-associated colorectal cancer by modulating the intestinal microbiota

Dengue virus infection increases microglial cell migration

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