How Turandot proteins protect Drosophila from autoimmune attacks

Drosophila melanogaster continues to be a goldmine of discovery.

In a recent study, researchers at EPFL have unveiled how a family of stress-induced proteins, known as the Turandots, protect the Drosophila respiratory system from its own immune self-attack, specifically against its own antimicrobial peptides (AMPs).

AMPs are small, cationic, and typically amphipathic peptides that play a crucial role in the innate immune defense in plants and animals. They kill or inhibit the growth of pathogens by disrupting their cell membranes. However, this defense mechanism comes with a downside: overproduction of AMPs can inadvertently damage the host organism’s cells, posing a risk to the organism itself.

The researchers at EPFL discovered that Turandot proteins act as a safeguard, binding to the host cell membranes, particularly in the respiratory system, to shield them from AMP-induced damage. Under stress conditions, Turandots target the respiratory epithelium, where they bind to and conceal phosphatidylserine, a negatively charged phospholipid. This lipid is prominently exposed on the outer layer of tracheal cell membranes and attracts AMPs. By masking phosphatidylserine, Turandots prevent AMPs from reaching the membrane, thereby averting cell lysis triggered by AMPs.

Flies deficient in Turandot genes exhibit increased vulnerability to stress, underscoring the proteins’ importance in stress resistance. Lipid bilayer recording experiments, performed with the Orbit 16 TC system, demonstrated that by binding to host cell membranes, Turandot proteins effectively prevent AMPs from forming harmful pores in the membranes, showcasing a novel aspect of immune regulation where the host mitigates potential damage from its own defense strategies.

These findings not only deepen our understanding of immune protection in Drosophila but also suggest potential implications for other organisms, including humans. By shedding light on the functions of Turandot proteins, this research opens new avenues for therapeutic strategies in human medicine, especially for conditions where tissue damage is a consequence of the body’s immune response.

For more details, please refer to the paper here: A humoral stress response protects Drosophila tissues from antimicrobial peptides

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