Immunity system complexity: fungal spore defense (Introduction)

by David Turell , Wednesday, June 21, 2023, 02:54 (311 days ago) @ David Turell

How the spores fight our system:

https://www.the-scientist.com/news-opinion/fungal-spores-hijack-a-host-protein-to-escap...

"A. fumigatus dodges the host immune system by sneaking into cells in membrane-enclosed vesicles known as phagosomes. These pathogen-containing vesicles are usually headed for degradation as the phagosomes mature and become more acidified. For A. fumigatus, though, intracellular extermination is not a done deal.

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"In a recent study, researchers discovered that A. fumigatus spores redirect fungus-containing phagosomes from a degradative to a non-degradative pathway by hijacking a human protein in those vesicles. They also found that transplant patients with a particular mutation in the gene that encodes the protein were less likely to develop invasive aspergillosis, a severe fungal infection with a high mortality rate among immunocompromised patients. The findings were published in the journal

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"To uncover A. fumigatus’s escape mechanism, the team assessed how the fungal spore proteins interacted with human lung epithelial cells, the body’s first line of defense against the mold. They showed that A. fumigatus spores use a surface protein, HscA, to bind to epithelial cells and that HscA was key to keeping the phagosomes in an immature state—less acidified vesicles that are not headed for degradation.

"They next showed that HscA targets a small human protein found in phagosomes, which the researchers named p11. By interacting with p11, A. fumigatus spores alter the molecular marks on the phagosomes, excluding a mark for vesicle destruction and recruiting tags for phagosome recycling. In turn, this leads the vesicle to be released into the extracellular space, transferred to an adjacent cell, or to stay inside the cells.

"For Scott Filler, a researcher at the University of California, Los Angeles, who was not involved in the study, the identification of HscA is a key finding. “This protein on the Aspergillus surface…basically stalls phagosome maturation,” he said.

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"To assess whether the in vitro findings were also clinically relevant, the researchers screened a group of stem cell transplant recipients and their corresponding donors for single nucleotide polymorphisms (SNP) in the p11 gene and evaluated their risk for developing invasive pulmonary aspergillosis (IPA). They found that a specific SNP located in a noncoding region of the p11 gene associated with a decreased risk for IPA. The fact that the researchers looked at patients to substantiate their in vitro findings makes the study stand out, said Filler. “It is very nice to go all the way from an in vitro model into basically human patients.”

"The findings not only uncover the different components used by A. fumigatus to dodge intracellular destruction in the host’s cells, but they also provide clinical evidence that may help identify patients at greater risk for fungal infections who would benefit the most from antifungal treatments."

Comment: The amazing battles continue. It is still a dog-eat-dog world with each side capable of adapting.