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The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells

ABSTRACT: Conventional dendritic cells (cDCs) generate protective cytotoxic T lymphocyte (CTL) responses against pathogens and tumours. This is achieved through a process known as cross-presentation (XP) and, despite its obvious biological importance, the mechanism(s) driving XP remain unclear. Here, we show that a cDC-specific pore-forming protein called apolipoprotein L 7C (APOL7C) is upregulated in response to innate immune stimuli and is recruited to phagosomes. Strikingly, its association with phagosomes leads to phagosomal rupture. This allows for the escape of engulfed antigens to the cytosol where they can be processed via the endogenous MHC class I antigen processing pathway. Accordingly, mice deficient in APOL7C do not efficiently prime CD8+ T cells in response to immunization with bead-bound and cell-associated antigens. Altogether, our data indicate the presence of dedicated apolipoproteins that mediate the delivery of phagocytosed proteins to the cytosol of activated cDCs to facilitate XP.

ORGANISM(S): Mus musculus

PROVIDER: GSE276376 | GEO | 2024/09/25

REPOSITORIES: GEO

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