Cargando…

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

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 cytokine...

Descripción completa

Detalles Bibliográficos
Autores principales: Mehrani, Yeganeh, Knapp, Jason P., Kakish, Julia E., Tieu, Sophie, Javadi, Helia, Chan, Lily, Stegelmeier, Ashley A., Napoleoni, Christina, Bridle, Byram W., Karimi, Khalil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531704/
https://www.ncbi.nlm.nih.gov/pubmed/37762443
http://dx.doi.org/10.3390/ijms241814141
_version_ 1785111782045515776
author Mehrani, Yeganeh
Knapp, Jason P.
Kakish, Julia E.
Tieu, Sophie
Javadi, Helia
Chan, Lily
Stegelmeier, Ashley A.
Napoleoni, Christina
Bridle, Byram W.
Karimi, Khalil
author_facet Mehrani, Yeganeh
Knapp, Jason P.
Kakish, Julia E.
Tieu, Sophie
Javadi, Helia
Chan, Lily
Stegelmeier, Ashley A.
Napoleoni, Christina
Bridle, Byram W.
Karimi, Khalil
author_sort Mehrani, Yeganeh
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10531704
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-105317042023-09-28 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, Yeganeh Knapp, Jason P. Kakish, Julia E. Tieu, Sophie Javadi, Helia Chan, Lily Stegelmeier, Ashley A. Napoleoni, Christina Bridle, Byram W. Karimi, Khalil Int J Mol Sci Article 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. MDPI 2023-09-15 /pmc/articles/PMC10531704/ /pubmed/37762443 http://dx.doi.org/10.3390/ijms241814141 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mehrani, Yeganeh
Knapp, Jason P.
Kakish, Julia E.
Tieu, Sophie
Javadi, Helia
Chan, Lily
Stegelmeier, Ashley A.
Napoleoni, Christina
Bridle, Byram W.
Karimi, Khalil
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531704/
https://www.ncbi.nlm.nih.gov/pubmed/37762443
http://dx.doi.org/10.3390/ijms241814141
work_keys_str_mv AT mehraniyeganeh murinemastcellsthataredeficientinifnarsignalingrespondtoviralinfectionbyproducingalargeamountofinflammatorycytokinesalowlevelofreactiveoxygenspeciesandahighrateofcelldeath
AT knappjasonp murinemastcellsthataredeficientinifnarsignalingrespondtoviralinfectionbyproducingalargeamountofinflammatorycytokinesalowlevelofreactiveoxygenspeciesandahighrateofcelldeath
AT kakishjuliae murinemastcellsthataredeficientinifnarsignalingrespondtoviralinfectionbyproducingalargeamountofinflammatorycytokinesalowlevelofreactiveoxygenspeciesandahighrateofcelldeath
AT tieusophie murinemastcellsthataredeficientinifnarsignalingrespondtoviralinfectionbyproducingalargeamountofinflammatorycytokinesalowlevelofreactiveoxygenspeciesandahighrateofcelldeath
AT javadihelia murinemastcellsthataredeficientinifnarsignalingrespondtoviralinfectionbyproducingalargeamountofinflammatorycytokinesalowlevelofreactiveoxygenspeciesandahighrateofcelldeath
AT chanlily murinemastcellsthataredeficientinifnarsignalingrespondtoviralinfectionbyproducingalargeamountofinflammatorycytokinesalowlevelofreactiveoxygenspeciesandahighrateofcelldeath
AT stegelmeierashleya murinemastcellsthataredeficientinifnarsignalingrespondtoviralinfectionbyproducingalargeamountofinflammatorycytokinesalowlevelofreactiveoxygenspeciesandahighrateofcelldeath
AT napoleonichristina murinemastcellsthataredeficientinifnarsignalingrespondtoviralinfectionbyproducingalargeamountofinflammatorycytokinesalowlevelofreactiveoxygenspeciesandahighrateofcelldeath
AT bridlebyramw murinemastcellsthataredeficientinifnarsignalingrespondtoviralinfectionbyproducingalargeamountofinflammatorycytokinesalowlevelofreactiveoxygenspeciesandahighrateofcelldeath
AT karimikhalil murinemastcellsthataredeficientinifnarsignalingrespondtoviralinfectionbyproducingalargeamountofinflammatorycytokinesalowlevelofreactiveoxygenspeciesandahighrateofcelldeath