کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5921618 | 1571001 | 2014 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Forkhead, a new cross regulator of metabolism and innate immunity downstream of TOR in Drosophila Forkhead, a new cross regulator of metabolism and innate immunity downstream of TOR in Drosophila](/preview/png/5921618.png)
- Antimicrobial peptide (AMP) expression is regulated by nutrient signaling (IlS and TOR).
- The FKH-dependent regulation of AMPs occurs upon downregulation of TOR.
- The FKH transcription factor regulates a defined subset of AMPs.
- Nuclear-cytoplasmic shuttling of FKH in response to TOR inhibition occurs in the midgut.
Antimicrobial peptides (AMPs) are conserved cationic peptides which act both as defense molecules of the host immune system and as regulators of the commensal microbiome. Expression of AMPs is induced in response to infection by the Toll and Imd pathway. Under non-infected conditions, the transcription factor dFOXO directly regulates a set of AMP expression at low levels when nutrients are limited.Here we have analyzed whether target of rapamycin (TOR), another major regulator of growth and metabolism, also modulates AMP responses in Drosophila. We found that downregulation of TOR by feeding the drug rapamycin or by overexpressing the negative TOR regulators TSC1/TSC2, resulted in a specific induction of the AMPs Diptericin (Dpt) and Metchnikowin (Mtk). In contrast, overexpression of Rheb, which positively regulates TOR led to a repression of the two AMPs. Genetic and pharmacological experiments indicate that Dpt and Mtk activation is controlled by the transcription factor Forkhead (FKH), the founding member of the FoxO family. Shuttling of FKH from the cytoplasm to the nucleus is induced in the fat body and in the posterior midgut in response to TOR downregulation. The FKH-dependent induction of Dpt and Mtk can be triggered in dFOXO null mutants and in immune-compromised Toll and IMD pathway mutants indicating that FKH acts in parallel to these regulators.Together, we have discovered that FKH is the second conserved member of the FoxO family cross-regulating metabolism and innate immunity. dFOXO and FKH, which are activated upon downregulation of insulin or TOR activities, respectively, act in parallel to induce different sets of AMPs, thereby modulating the immune status of metabolic tissues such as the fat body or the gut in response to the oscillating energy status of the organism.
Journal: Journal of Insect Physiology - Volume 69, October 2014, Pages 80-88