A humoral stress response protects Drosophila tissues from antimicrobial peptides

Rommelaere, S.; Carboni, A.; Bada Juarez, J. F.; Boquete, J.-P.; Abriata, L. A.; Teixeira Pinto Meireles, F.; Rukes, V.; Vincent, C. M.; Kondo, S.; Dionne, M. S.; Dal Peraro, M.; Cao, C.; Lemaitre, B.

doi:10.1101/2023.07.24.550293

bioRxiv · 10.1101/2023.07.24.550293

A humoral stress response protects Drosophila tissues from antimicrobial peptides

Rommelaere, S.·Carboni, A.·Bada Juarez, J. F.·Boquete, J.-P.·Abriata, L. A.·Teixeira Pinto Meireles, F.·Rukes, V.·Vincent, C. M.·Kondo, S.·Dionne, M. S.·Dal Peraro, M.·Cao, C.·Lemaitre, B.

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Abstract

The immune response against an invading pathogen is generally associated with collateral tissue damage caused by the immune system itself. Consequently, several resilience mechanisms have evolved to attenuate the negative impacts of immune effectors. Antimicrobial peptides (AMPs) are small, cationic peptides that contribute to innate defenses by targeting negatively charged membranes of microbes1, 2. While being protective against pathogens, AMPs can be cytotoxic to host cells1, 3. Little is known of mechanisms that protect host tissues from AMP-induced immunopathology. Here, we reveal that a family of stress-induced proteins, the Turandots4, 5, protect Drosophila host tissues from AMPs, increasing resilience to stress. Deletion of several Turandot genes increases fly susceptibility to environmental stresses due to trachea apoptosis and poor oxygen supply. Tracheal cell membranes expose high levels of phosphatidylserine, a negatively charged phospholipid, sensitizing them to the action of AMPs. Turandots are secreted from the fat body upon stress and bind to tracheal cells to protect them against AMPs. In vitro, Turandot A binds to phosphatidylserine on membranes and inhibits the pore-forming activity of Drosophila and human AMPs on eukaryotic cells without affecting their microbicidal activity. Collectively, these data demonstrate that Turandot stress proteins mitigate AMP cytotoxicity to host tissues and therefore improve their efficacy. This provides a first example of a humoral mechanism used by animals limiting host-encoded AMP collateral damages.

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Rommelaere, S., Carboni, A., Bada Juarez, J. F., Boquete, J.-P., Abriata, L. A., Teixeira Pinto Meireles, F., Rukes, V., Vincent, C. M., Kondo, S., Dionne, M. S., Dal Peraro, M., Cao, C., Lemaitre, B.. 2023-07-24. A humoral stress response protects Drosophila tissues from antimicrobial peptides. https://doi.org/10.1101/2023.07.24.550293

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