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ROS play a dual role in modulation of inflammatory outcome by Vibrio vulnificus adhesin OmpU via PI3K independent Akt activation in dendritic cells 2792

Year: 2025
Type: article
Abstract: Description The role of reactive oxygen species (ROS) is well established as a central player to inflammation progression. OmpU, an outer-membrane protein and a key virulence factor of Vibrio vulnificus, induces huge amount of ROS and pro-inflammatory responses in dendritic cells (DCs). In addition to pro-inflammatory responses V. vulnificus OmpU (VvOmpU) induces anti-inflammatory responses. Interestingly, we observed that ROS regulates both pro-inflammatory (IL-6, TNFa) as well as anti-inflammatory (IL-10) cytokine production, suggesting dual nature of ROS in promoting and regulating inflammation in DCs in response to VvOmpU. We observed that VvOmpU-induced pro- and anti-inflammatory responses in DCs are MyD88-dependent, involving TLR2 and TLR4, which also mediate NOX2-driven ROS generation. Further, downstream to TLRs MAPKs p38 and ERK are involved in VvOmpU-mediated ROS generation in DCs. We have also observed that PI3K inhibits VvOmpU-mediated ROS generation, but Akt induces it. Generally, PI3K acts upstream to Akt, but in VvOmpU-treated DCs Akt activation seems to be happening via a different pathway.Our further investigation revealed that intracellular Ca2+signaling, which also triggers VvOmpU induced ROS, probably activate Akt in a PI3K independent manner. Our results suggest that ROS could play a central role in a complex regulatory network that balances inflammatory responses in DCs in response to bacterial virulence factor. Funding Sources This work is supported by IISER Mohali Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)
DOI: 10.1093/jimmun/vkaf283.673
Language: English
Subfield: Immunology
Open Access status: bronze
OpenAlex ID: W4416446646
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