Biology Department, New Mexico State University, Las Cruces, NM, 88003, USA.
Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM, 88003, USA.
Sci Rep. 2022 Apr 9;12(1):6005. doi: 10.1038/s41598-022-09817-2.
Immune responses require delicate controls to maintain homeostasis while executing effective defense. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor. The Krüppel-like factor 10 (KLF10) is a C2H2 zinc-finger containing transcription factor. The functions of mosquito AhR and KLF10 have not been characterized. Here we show that AhR and KLF10 constitute a transcriptional axis to modulate immune responses in mosquito Anopheles gambiae. The manipulation of AhR activities via agonists or antagonists repressed or enhanced the mosquito antibacterial immunity, respectively. KLF10 was recognized as one of the AhR target genes in the context. Phenotypically, silencing KLF10 reversed the immune suppression caused by the AhR agonist. The transcriptome comparison revealed that silencing AhR and KLF10 plus challenge altered the expression of 2245 genes in the same way. The results suggest that KLF10 is downstream of AhR in a transcriptional network responsible for immunomodulation. This AhR-KLF10 axis regulates a set of genes involved in metabolism and circadian rhythms in the context. The axis was required to suppress the adverse effect caused by the overactivation of the immune pathway IMD via the inhibitor gene Caspar silencing without a bacterial challenge. These results demonstrate that the AhR-KLF10 axis mediates an immunoregulatory transcriptional network as a negative loop to maintain immune homeostasis.
免疫反应需要精细的控制来维持体内平衡，同时执行有效的防御。芳香烃受体 (AhR) 是一种配体激活的转录因子。Krüppel 样因子 10 (KLF10) 是一种含有 C2H2 锌指的转录因子。蚊子 AhR 和 KLF10 的功能尚未得到表征。在这里，我们表明 AhR 和 KLF10 构成了一个转录轴，以调节蚊子疟原虫的免疫反应。通过激动剂或拮抗剂操纵 AhR 活性分别抑制或增强了蚊子的抗菌免疫。KLF10 被认为是 AhR 靶基因之一。表型上，沉默 KLF10 逆转了 AhR 激动剂引起的免疫抑制。转录组比较显示，沉默 AhR 和 KLF10 加挑战以相同的方式改变了 2245 个基因的表达。结果表明，KLF10 是负责免疫调节的转录网络中 AhR 的下游。在该背景下，该轴调节了一组参与代谢和昼夜节律的基因。该轴被要求通过抑制基因 Caspar 沉默来抑制免疫途径 IMD 过度激活引起的不利影响，而无需细菌挑战。这些结果表明，AhR-KLF10 轴作为一个负反馈环介导免疫调节转录网络来维持免疫稳态。
