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.
Look out for the associated commentary to follow in PLoS Biology by David Schneider of Stanford University, entitled "How and Why Does a Fly Turn Its Immune System Off""
Citation: Kim LK, Choi UY, Cho HS, Lee JS, Lee WB, et al. (2007) Down-regulation of NF-jB target genes by the AP-1 and STAT complex during the innate immune response in Drosophila. PLoS Biol 5(9): e238. doi:10.1371/journal.pbio.0050238.
Seoul, Seoul 120-749
Republic of Korea
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