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Lookup NU author(s): Dr Tiaan Heunis, Dr Jose Luis Marin-RubioORCiD, Francesca Cianfanelli, Dr Ben RaymondORCiD, Dr Joe Inns, Dr Julien Peltier, Professor Fiona OakleyORCiD, Dr Anetta Svitorka Hartlova, Professor Matthias TrostORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
©2022 The Authors. Published under the terms of the CC BY 4.0 license.Phagocytosis is a key process in innate immunity and homeostasis. After particle uptake, newly formed phagosomes mature by acquisition of endolysosomal enzymes. Macrophage activation by interferon gamma (IFN-γ) increases microbicidal activity, but delays phagosomal maturation by an unknown mechanism. Using quantitative proteomics, we show that phagosomal proteins harbour high levels of typical and atypical ubiquitin chain types. Moreover, phagosomal ubiquitylation of vesicle trafficking proteins is substantially enhanced upon IFN-γ activation of macrophages, suggesting a role in regulating phagosomal functions. We identified the E3 ubiquitin ligase RNF115, which is enriched on phagosomes of IFN-γ activated macrophages, as an important regulator of phagosomal maturation. Loss of RNF115 protein or ligase activity enhanced phagosomal maturation and increased cytokine responses to bacterial infection, suggesting that both innate immune signalling from the phagosome and phagolysosomal trafficking are controlled through ubiquitylation. RNF115 knock-out mice show less tissue damage in response to S. aureus infection, indicating a role of RNF115 in inflammatory responses in vivo. In conclusion, RNF115 and phagosomal ubiquitylation are important regulators of innate immune functions during bacterial infections.
Author(s): Bilkei-Gorzo O, Heunis T, Marin-Rubio JL, Cianfanelli FR, Raymond BBA, Inns J, Fabrikova D, Peltier J, Oakley F, Schmid R, Hartlova A, Trost M
Publication type: Article
Publication status: Published
Journal: EMBO Journal
Year: 2022
Volume: 41
Issue: 23
Print publication date: 01/12/2022
Online publication date: 25/10/2022
Acceptance date: 06/10/2022
Date deposited: 07/11/2022
ISSN (print): 0261-4189
ISSN (electronic): 1460-2075
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.15252/embj.2021108970
DOI: 10.15252/embj.2021108970
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