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Phagosomes are competent organelles for antigen cross-presentation

Abstract

The ability to process microbial antigens and present them at the surface of cells is an important aspect of our innate ability to clear infections. It is generally accepted that antigens in the cytoplasm are loaded in the endoplasmic reticulum and presented at the cell surface on major histocompatibility complex (MHC) class I molecules, whereas peptides present in endo/phagocytic compartments are presented on MHC class II molecules1,2. Despite the apparent segregation of the class I and class II pathways, antigens from intracellular pathogens including mycobacteria, Escherichia coli, Salmonella typhimurium, Brucella abortus and Leishmania, have been shown to elicit an MHC class-I-dependent CD8+ T-cell response3,4,5,6,7, a process referred to as cross-presentation2. The cellular mechanisms allowing the cross-presentation pathway are poorly understood. Here we show that phagosomes display the elements and properties needed to be self-sufficient for the cross-presentation of exogenous antigens, a newly ascribed function linked to phagocytosis mediated by the endoplasmic reticulum.

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Figure 1: Exogenous proteins internalized by phagocytosis are retrotranslocated to the cytoplasmic side of phagosomes.
Figure 2: Proteasomes are present on phagosomes.
Figure 3: Ubiquitinated proteins associate with proteasomes on the cytoplasmic side of phagosomes.
Figure 4: Exogenous proteins loaded in phagosomes can be presented by MHC class I complexes at the surface of macrophages and trigger a TAP-dependent CD8+ T-cell response.

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Acknowledgements

We thank C. Rondeau, S. Tessier and A. Carrier for technical assistance and G. Milon for discussions. We thank K. Rock for the BMA3.1A and BMC2 cell lines. We also thank D. Boismenu and J. Bergeron from the Montreal Proteomics Network for help with the mass spectrometry analyses of the blue native gel samples. This work was supported by the Canadian Institute for Health Research, Genome Canada/Québec (M.D.), and the NIH (D.S.).

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Correspondence to Michel Desjardins.

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Houde, M., Bertholet, S., Gagnon, E. et al. Phagosomes are competent organelles for antigen cross-presentation. Nature 425, 402–406 (2003). https://doi.org/10.1038/nature01912

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