Drosophila Relish‐mediated miR‐317 expression facilitates immune homeostasis restoration via inhibiting PGRP‐LC

Abstract

Innate immunity is the first and essential line for resisting pathogens, and the immune intensity and duration need to be strictly regulated to balance excessive or insufficient immune response. MicroRNAs (miRNAs) are crucial regulators of immune response in Drosophila, yet how immune-related miRNAs are regulated remains poorly understood. Herein, we elucidated that the involvement of miR-317 in NF-κB transcription factor Relish mediated Drosophila Imd pathway in response to Gram-negative (G-) bacteria stimulation. Remarkably, the dynamic expression profiling for immune response indicated that Relish simultaneously enhances the expression of the effector antimicrobial peptide Dpt as well as miR-317 post-infection. Upregulation of miR-317 could further down-regulate the expression of PGRP-LC, thereby forming a feedback in Drosophila Imd pathway to prevent over-activation and restore immune homeostasis. Taken together, our study not only uncovers a novel Relish/miR-317/PGRP-LC regulatory axis to attenuate Drosophila Imd immune response and facilitate immune homeostasis restoration, but also provides vital insights into the complex mechanisms of animal innate immune regulation.

miR-317-3p and miR-283-5p Play a Crucial Role in Regulating the Resistance to Indoxacarb in Spodoptera frugiperda by Targeting GSTs4

“…57−59 For example, miR-317-3p plays crucial roles in Drosophila innate immunity, where it directly targets PGRP-LC and AMPs, forming negative feedback to restore immune homeostasis during the Drosophila Imd immune pathway. 60 While there is no prior research on the effects of miR-317-3p and miR-283-5p on insecticide resistance, our results demonstrate that both miR-317-3p and miR-283-5p can downregulate the expression of GSTs4 and mediate the resistance development of S. frugiperda to indoxacarb. The data of dual-luciferase reporter assays showed that both cotransfection of the agomir of miR-317-3p and miR-283-5p with the wild type of pmirGLO constructions significantly decreases the relative luciferase activity compared to the NC agomir group, while no significant differences were observed when cotransfecting their agomirs with mutated pmirGLO constructions (Figure 4C,D).…”

“…miR-317-3p is a highly conserved miRNA and has been found to participate in various life processes in Drosophila . − For example, miR-317-3p plays crucial roles in Drosophila innate immunity, where it directly targets PGRP-LC and AMPs, forming negative feedback to restore immune homeostasis during the Drosophila Imd immune pathway . While there is no prior research on the effects of miR-317-3p and miR-283-5p on insecticide resistance, our results demonstrate that both miR-317-3p and miR-283-5p can downregulate the expression of GSTs4 and mediate the resistance development of S.…”

Integrated Analysis of MicroRNA and mRNA Expression Profiles in the Fat Bodies of MbMNPV-Infected Helicoverpa armigera

“…A total of 52 DEmiRNAs were obtained, of which 24 were upregulated and 28 were downregulated. Of these miRNAs, bmo-miR-1175-3p [ 21 ], miR-12 [ 22 ], miR-92b [ 23 ], miR-34 [ 24 ], miR-927 [ 25 ], miR-281 [ 26 ], miR-927 [ 25 ], and miR-317 [ 27 ] have been reported in previous studies and known to be related to virus infection. Reports suggest that one specific miRNA can regulate the expression of multiple mRNAs and vice versa [ 28 ].…”

MicroRNAs reshape the immunity of insects in response to bacterial infection

“…Collectively, miR-317 forms an axis with other effectors that is known as the Relish/miR-317/PGRP-LC axis to restore immune homeostasis and negative feedback regulation of the IMD immune response in Drosophila. Additionally, miR-317 has the ability to suppress the over-activation of IMD immune functions and to restore immune homeostasis (Figure 5) (58).…”