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The E3 ubiquitin ligase RNF115 regulates phagosome maturation and host response to bacterial infection

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.

Publication metadata

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


DOI: 10.15252/embj.2021108970


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Funder referenceFunder name
215542/Z/19/ZWellcome Trust
FO is funded by Medical Research Council program grants MR/K0019494/1 and MR/R023026/1.
FRC is a Marie Sklodowska Curie Fellow within the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 892252.
Medical Research Council UK (MC_UU_12016/5)
MR/R023026/1Medical Research Council (MRC)
Newcastle University start-up funding
Wellcome Trust Investigator Award to MT (215542/Z/19/Z).