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Human p11-mediated re-direction of phagosomes to the recycling endosome-expulsion pathway induced by fungal pathogen

ABSTRACT: Aspergillus fumigatus invades pulmonary epithelial cells by induced phagocytosis, and survives for some time in phagosomes. Although dihydroxynaphthalene melanin on fungal conidia has been intensively investigated for its role in inhibiting phagosome maturation, a proportion of melanin-lacking mutant conidia still escaped killing by phagosomes, implying that additional mechanisms must be in place. Here, we identified the fungal surface-exposed heat shock protein HscA as an effector protein that binds the human p11 protein. A. fumigatus induces and increases the amount of p11 and anchors p11 and Annexin A2 to phagosomes and phagocytic cups, the latter facilitates phagocytosis of conidia by epithelial cells. We identified a SNP in the in the non-coding region of the human p11 gene resulting in heightened susceptibility for invasive aspergillosis in hematopoietic stem-cell transplant recipients. This finding can help for stratification of donors for hematopoietic stem cell transplantation. On phagosomes, HscA triggers an increase of p11 on the phagosomal membrane, which prevents directing the phagosome to the degradative pathway by re-directing the p11-positive phagosome to the recycling endosomal pathway. Therefore, a surface-located heat shock protein enables fungal conidia to escape phagolysosome killing.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Neosartorya Fumigata (aspergillus Fumigatus) Homo Sapiens (human)

SUBMITTER: Thomas Krüger

LAB HEAD: Axel A. Brakhage

PROVIDER: PXD030501 | Pride | 2023-03-13

REPOSITORIES: Pride

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