Production of IL-8, IL-17, IFN-gamma and IP-10 in human astrocytes correlates with alphavirus attenuation

Peng, Bi-Hung; Borisevich, Viktoriya; Popov, Vsevolod L.; Zacks, Michele A.; Estes, D. Mark; Campbell, Gerald A.; Paessler, Slobodan

doi:10.1016/j.vetmic.2012.11.021

Cited by 11 publications

(16 citation statements)

References 66 publications

(74 reference statements)

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“…By 48hpi only 20% of the cells or less were viable at all MOIs. These results are in agreement with previous studies demonstrating the ability of VEEV to productively infect primary astrocytes (Peng et al, 2013;Schoneboom et al, 1999).…”

Section: Replication Of Veev In Human Primary Astrocytessupporting

confidence: 94%

“…In this study, we showed that VEEV replication in human primary astrocytes and the apoptosis induced following VEEV infection can be suppressed by blocking either ERK or PERK pathways, both of which are responsible for upregulating EGR1 pathway, rescuing the cells from VEEV induced apoptosis. Cytopathic effects in primary astrocytes following VEEV infection has been shown in previous published studies (Peng et al, 2013;Schoneboom et al, 1999). Substantial amounts of astrocyte cell death due to VEEV-astrocyte interaction could contribute to decreased neuronal survival and long-term CNS damage.…”

Section: Discussionmentioning

confidence: 70%

“…Infection of primary astrocytes with VEEV subtype IAB V3000 (molecular clone of VEEV TrD (Grieder et al, 1995)) or attenuated V3010 (cloned avirulent mutant, E2 76Glu to Lys (Aronson et al, 2000)) released pro-inflammatory cytokines, TNF-α, and iNOS. The attenuated TC-83 strain of VEEV induces pro-inflammatory cytokines such as IFN-Ɣ, IL-1β, IL-6, IL-8, IL-12, and TNF-α, which contribute to the inflammatory microenvironment (Peng et al, 2013;Schoneboom et al, 2000).…”

Section: Venezuelan Equine Encephalitis Virus (Veev) Is An Encephalitmentioning

confidence: 99%

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EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death

et al. 2020

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Section: Replication Of Veev In Human Primary Astrocytessupporting

confidence: 94%

Section: Discussionmentioning

confidence: 70%

Section: Venezuelan Equine Encephalitis Virus (Veev) Is An Encephalitmentioning

confidence: 99%

See 1 more Smart Citation

EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death

et al. 2020

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“…The attenuated TC-83 strain is known to induce pro-inflammatory cytokines such as interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-8, IL-12, and tumor necrosis factor -α (TNF-α) [25–28]. These potent pro-inflammatory cytokines control several downstream targets which contribute to the inflammatory microenvironment.…”

Section: Introductionmentioning

confidence: 99%

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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“…In addition to T cells, cells other than T and NK cells need to produce this cytokine to prevent reactivation of the infection in the brain (2). Microglia and astrocytes from the brain have been shown to produce IFN-γ in vitro in response to various stimulations including LPS (3, 4). However, it is unknown whether IFN-γ produced by brain-resident cells including glial cells plays any roles in resistance to cerebral infections with microorganisms including T. gondii .…”

Section: Introductionmentioning

confidence: 99%

Cutting Edge: IFN-γ Produced by Brain-Resident Cells Is Crucial To Control Cerebral Infection with Toxoplasma gondii

Ochiai

Tiwari

et al. 2015

The Journal of Immunology

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In vitro studies demonstrated that microglia and astrocytes produce IFN-γ in response to various stimulations including LPS. However, the physiological role of IFN-γ production by brain-resident cells including glial cells in resistance against cerebral infections remains unknown. We analyzed the role of IFN-γ production by brain-resident cells in resistance to reactivation of cerebral infection with Toxoplasma gondii using a murine model. Our study using bone marrow chimeric mice revealed that IFN-γ production by brain-resident cells is essential for upregulating IFN-γ-mediated protective innate immune responses to restrict cerebral T. gondii growth. Studies using a transgenic strain that expresses IFN-γ only in CD11b+ cells suggested that IFN-γ production by microglia, which is the only CD11b+ cell population among brain-resident cells, is able to suppress the parasite growth. Furthermore, IFN-γ produced by brain-resident cells is pivotal for recruiting T cells into the brain to control the infection. These results indicate that IFN-γ produced by brain-resident cells is crucial for facilitating both the protective innate and T cell-mediated immune responses to control cerebral infection with T. gondii.

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Production of IL-8, IL-17, IFN-gamma and IP-10 in human astrocytes correlates with alphavirus attenuation

Cited by 11 publications

References 66 publications

EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death

EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death

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

Cutting Edge: IFN-γ Produced by Brain-Resident Cells Is Crucial To Control Cerebral Infection with Toxoplasma gondii

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