Gelsolin protects mitochondria and regulates inflammation during Legionella pneumophila infection

Authors

Whitham, O. D., Eltobgy, M., Shamseldin, M. M., Badr, A., Perez, R. A., Hassan, Y., Amer, H. M., Gupta, G., Faber, S. E., Robledo-Avila, F. H., Zhang, X., Mikami, M., Partida-Sanchez, S., Seveau, S., Amer, A.

Abstract

Legionella pneumophila (L. pneumophila) is the causative agent of Legionnaires' disease, a severe bacterial pneumonia. Difficulty in diagnosing Legionnaires' disease leads to an underreporting of cases and delayed treatment. Rapid-acting, broad-spectrum therapies are needed to treat pathology while avoiding antibiotic resistance. We showed that gelsolin knockout (gsn-/-) mice succumb more quickly to severe L. pneumophila infection despite no difference in bacterial loads in the lung compared to wild type mice. There is an increase in CXCL1/KC production from macrophages from gsn-/- mice, which is accompanied by increased neutrophils and apoptosis in their lungs. Neutrophils lacking gelsolin produce fewer neutrophil extracellular traps, and their mitochondrial capacity is diminished in response to L. pneumophila. Gelsolin is required for maintaining mitochondrial network morphology and respiration in L. pneumophila infected macrophages. When given recombinant gelsolin protein, gsn-/- mice survive significantly longer during severe L. pneumophila infection, with reduced lung pathology, and the inflammatory signature of their macrophages was reduced in vitro. Together, gelsolin protects mice during severe L. pneumophila infection, dampens inflammation, promotes mitochondrial health, and maintains neutrophil function.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 21 Aug 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.