Flies can turn off their immune response

Sep 4 2007

The immune response is actively turned on to target and destroy foreign infectious elements, but in the interests of self-preservation, it is just as important to turn the immune system off to avoid damage to oneself by "friendly fire."

The fruit fly Drosophila has served as a good model for the induction of an innate immune response, pointing to conserved pathways and mechanisms. Recent work shows that the fly's immune response is more subtly regulated and produces a wider range of responses than was thought possible even just a few years ago. In a study to be published this week in the premier open-access journal PLoS Biology, Young-Joon Kim and colleagues from Seoul, Korea show that the fly immune response is edited and repressed.

The authors report a mechanism of control that relies on the transcription factors AP-1 and STAT to prevent the excessive activation of the NF-êB–mediated immune response. Thus, AP-1 and STAT, renowned for their role in activating the NF-êB–mediated immune response, appear also to participate in its attenuation. In their role as negative regulators, AP-1 and STAT form a complex HMG protein and HDAC, proteins known to be involved in DNA bending and chromatin structure. This complex is then recruited to the promoter regions of NF-êB target genes, causing the chromatin structure near the NF-êB target genes to contract and the expression of NF-êB target genes to shut down. Kim and colleagues found that mis-regulation of this negative-feedback process increased the lethality of bacterial infection in Drosophila. In mammals, over-activated NF-êB–mediated immune responses can manifest in a utoimmune disease. Thus, feedback inhibition of NF-êB appears to be evolutionarily conserved to maintain properly balanced immune responses.