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

ABSTRACT: Phagocytosis is an essential process for the microbicidal function of professional phagocytes, in which phagosome maturation plays a critical role. Macrophage activation by interferons (IFN) increases their microbicidal activity, but delays phagosomal maturation. Here, we investigated the role of ubiquitylation in phagosome functions. We show that phagosomal proteins are ubiquitylated and that phagosomes contain diverse ubiquitin chain types, including atypical ubiquitin chains. IFN-γ activation of macrophages substantially enhanced phagosomal ubiquitylation of both innate immune response proteins and vesicle trafficking proteins. 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 ubiquitin ligase activity facilitated enhanced phagosomal maturation, and increased cytokine responses to Staphylococcus aureus. Our data suggests that both innate immune signalling and phagolysosomal trafficking are controlled through ubiquitylation. In conclusion, we identify RNF115 and ubiquitylation as important regulators of innate immune signalling from the phagosome during bacterial infections.

INSTRUMENT(S): Orbitrap Fusion Lumos, Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Macrophage

SUBMITTER: Matthias Trost

LAB HEAD: Matthias Trost

PROVIDER: PXD026843 | Pride | 2022-07-20

REPOSITORIES: Pride

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