Gogoi, Mayuri ; Ravikumar, Visweswaran ; Dixit, Narendra M ; Chakravortty, Dipshikha (2018) Salmonella escapes antigen presentation through K63 ubiquitination mediated endosomal proteolysis of MHC II via modulation of endosomal acidification in dendritic cells Pathogens and Disease, 76 (2). ISSN 2049-632X
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Official URL: http://doi.org/10.1093/femspd/ftx125
Related URL: http://dx.doi.org/10.1093/femspd/ftx125
Abstract
CD4+ T-cell response is vital for successful clearance of Salmonella Typhimurium infection. Efficient antigen presentation is crucial for effective CD4+ T-cell response. Previous study has reported that Salmonella abrogates antigen presentation capacity of dendritic cells in order to escape host adaptive immune response. In this study, we have elucidated the mechanism of Salmonella-mediated downregulation of the total cellular Major Histocompatibility Complex (MHC) II pool in dendritic cells. Infected dendritic cells show upregulation of E3 ubiquitin ligase, MARCH1 expression and K63-linked ubiquitination of MHC II. Salmonella infection also enhances the internalisation of ubiquitin-tagged MHC II molecules that are subsequently degraded by endosomal proteases. In addition, Salmonella regulates the activation of endosomal proteases by lowering the pH of endosomes. In infected dendritic cells, Salmonella delays NOX2 recruitment to the phagosomes thereby preventing its alkalinisation. NOX2 is a significant part of innate immune response against pathogens as it is responsible for Reactive Oxygen Species (ROS) production. In this study, we have demonstrated how Salmonella evades MHC II-mediated adaptive immune response in dendritic cells through enhanced endosomal proteolysis. To escape host CD4+T response, Salmonella delays NOX2 recruitment, an innate immune response element to the phagosomes.
Item Type: | Article |
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Source: | Copyright of this article belongs to Oxford University Press. |
Keywords: | Dendritic Cells; T Cells; MHC Class II; Ubiquitination; Antigen Presentation/Processing. |
ID Code: | 118255 |
Deposited On: | 19 May 2021 11:23 |
Last Modified: | 02 Feb 2023 05:17 |
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