The ISCIII reveals how a cellular process shields a key immunity protein against a fungus

The ISCIII reveals how persulfidation protects calprotectin from oxidative damage and strengthens the immune defense against the fungus Aspergillus fumigatus.

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A study by the National Center for Microbiology of the Carlos III Health Institute (ISCIII) has managed to clarify how persulfidation protects calprotectin, an essential protein in the immune response, from the oxidative damage that occurs during infections caused by the fungus "Aspergillus fumigatus".

The findings, published in the journal "iScience", deepen understanding of how epithelial cells of the lung alveoli react to this opportunistic pathogenic fungus, capable of causing serious diseases in people with a compromised immune system.

The study, led by researcher Jorge Amich, from the CNM-ISCIII Reference Laboratory for Research in Mycology, has identified the proteins that undergo persulfidation as part of the response to infection by "A. fumigatus". The set of these proteins is called the persulfidome.

The scientific team has found that an important portion of these proteins is linked to transcription, RNA metabolism, and its translation, which reinforces the involvement of this process in protein synthesis and its subsequent activity.

Protection of calprotectin against oxidative stress

Among the proteins mentioned is calprotectin, made up of two small peptides and with a prominent role in the immune response to pathogenic microorganisms. The work shows that persulfidation shields this protein from oxidation and allows it to preserve its defensive functions against pathogens.

The authors emphasize that this mechanism is especially important because, during infection, the immune system exposes microorganisms to intense oxidative stress. Keeping calprotectin activity protected makes it possible for it to continue carrying out its role within the antimicrobial response.

Persulfidation is a post-translational modification, that is, a chemical change that occurs in proteins and allows their activity to be modulated and to respond quickly to different biological stimuli. Previous studies had already shown that this mechanism is key to orchestrating an effective immune response to infections such as those caused by Aspergillus fumigatus.