Contrary to acquired immunity which is a feature of mammals, innate immunity is a fast, non-specific reaction to external pathogens and is found in all animal organisms. In flies, it involves the activity of intestinal defenses, antimicrobial peptides and macrophage-like cells in the blood.

The screen took advantage of the Vienna Drosophila RNAi Library, a powerful tool of 22 000 strains of fruit flies located at the IMBA. The experiment included feeding the flies with the highly infectious bacterium Serratia marcescens to which immunocompetent flies usually succumb within six days. The researchers were able to switch off the fly’s genes one by one, using a standardized heat shock procedure as trigger.

In addition to previously known genes and pathways, the experiments revealed more than 800 additional genes involved in innate immunity, the majority of which had unknown function until now. Intriguingly, some ten percent of these genes seem to have a negative function against infection: when they were switched off, the infected flies actually lived longer than the expected six days, in some cases much longer. “This effect is a real power of our system”, comments Cronin. “We are very eager to find out what these candidates are doing”. For the other 90% of immune-compromised fruit flies, life was significantly shortened by one or two days.

Because of the high degree of conservation of innate immunity, the results are also relevant for immunologists interested in higher animals and humans. One of the next steps will therefore be to find out which of the isolated genes have relevance in the context of mammalian immunity.

The work was carried out in collaboration with Dominique Ferrandon and Nadine Nehme of the Institut de Biologie Moleculaire et Cellulaire du CNRS in Strasbourg.