An RNA interference screen identifies Inhibitor of Apoptosis Protein 2 as a regulator of innate immune signalling in Drosophila.

Innate immunity in vertebrates and invertebrates is of central importance as a biological programme for host defence against pathogenic challenges. To find novel components of the Drosophila immune deficiency (IMD) pathway in cultured haemocyte-like cells, we screened an RNA interference library for modifiers of a pathway-specific reporter. Selected modifiers were further characterized using an independent reporter assay and placed into the pathway in relation to known pathway components. Interestingly, the screen identified the Inhibitor of Apoptosis Protein 2 (IAP 2) as being required for IMD signalling. Whereas loss of DIAP 1, the other member of the IAP protein family in Drosophila, leads to apoptosis, we show that IAP 2 is dispensable for cell viability in haemocyte-like cells. Cell-based epistasis experiments show that IAP 2 acts at the level of Tak 1 (transforming growth factor-beta-activated kinase 1). Our results indicate that IAP gene family members may have acquired other functions, such as the regulation of the tumour necrosis factor-like IMD pathway during innate immune responses.