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

The decision whether endosomes in mammalian cells enter the degradative or non-degradative pathway is of fundamental importance for killing of ingested pathogens and an essential basic mechanism whose malfunctioning has pathological consequences. We discovered that the human p11 protein is a decisive factor for directing phagosomes either to the degradative or secretory pathway. The HscA protein present on the spore surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on the phagosome and thereby inhibits phagosome maturation that would result in for expulsion of spores. The clinical relevance of our findings is supported by the identification of an SNP in the non-coding region of the human p11 gene that affects its mRNA level and is associated with protection against invasive pulmonary aspergillosis. The mRNA of human lung epithelial H441 cells without or with A. fumigatus infection were sequenced