Disruption of Type I Interferon Signaling Causes Sexually Dimorphic Dysregulation of Anti-Viral Cytokines

Darzianiazizi, Maedeh; Allison, Katrina E.; Kulkarni, Raveendra R.; Sharif, Shayan; Karimi, Khalil; Bridle, Byram W.

doi:10.1016/j.cytox.2021.100053

Cited by 1 publication

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References 87 publications

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“…Viruses use various strategies to compromise these responses. We demonstrated that blocking IFN responses that were infected with rVSVΔm51 led to an imbalanced cytokine reaction, causing a delay in the elimination of the virus [ 12 ]. The protective mechanisms of type I IFN signaling from virus-induced cell death are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Murine Mast Cells That Are Deficient in IFNAR-Signaling Respond to Viral Infection by Producing a Large Amount of Inflammatory Cytokines, a Low Level of Reactive Oxygen Species, and a High Rate of Cell Death

Mehrani,

Knapp,

Kakish

et al. 2023

IJMS

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Mat cells (MCs) are located in the skin and mucous membranes at points where the body meets the environment. When activated, MCs release inflammatory cytokines, which help the immune system to fight viruses. MCs produce, and have receptors for interferons (IFNs), which belong to a family of cytokines recognized for their antiviral properties. Previously, we reported that MCs produced proinflammatory cytokines in response to a recombinant vesicular stomatitis virus (rVSVΔm51) and that IFNAR signaling was required to down-modulate these responses. Here, we have demonstrated that UV-irradiated rVSVΔm51 did not cause any inflammatory cytokines in either in vitro cultured mouse IFNAR-intact (IFNAR+/+), or in IFNAR-knockout (IFNAR−/−) MCs. However, the non-irradiated virus was able to replicate more effectively in IFNAR−/− MCs and produced a higher level of inflammatory cytokines compared with the IFNAR+/+ MCs. Interestingly, MCs lacking IFNAR expression displayed reduced levels of reactive oxygen species (ROS) compared with IFNAR+/+ MCs. Additionally, upon the viral infection, these IFNAR−/− MCs were found to coexist with many dying cells within the cell population. Based on our findings, IFNAR-intact MCs exhibit a lower rate of rVSVΔm51 infectivity and lower levels of cytokines while demonstrating higher levels of ROS. This suggests that MCs with intact IFNAR signaling may survive viral infections by producing cell-protective ROS mechanisms and are less likely to die than IFNAR−/− cells.

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Section: Introductionmentioning

confidence: 99%