ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1664564
This article is part of the Research TopicRegulation of Innate Immunity Response: from Drosophila to HumansView all 4 articles
The functional Mi-2/Foxo complex targets PGRP-SC2 for the Drosophila immune defense against bacterial infection
Provisionally accepted
- 1Fujian Medical University, Fuzhou, China
- 2Anhui Agricultural University, Hefei, China
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Innate immunity is orchestrated by an array of conserved signaling pathways and transcriptional regulators. While Forkhead box O (Foxo) has emerged as a pivotal transcription factor in regulating immune homeostasis, its interaction with chromatin remodeling machinery remains poorly defined. Here, we identify the chromatin remodeler Mi-2 as a crucial component of the Drosophila antibacterial immune defense. Silencing of Mi-2 abrogates the induction of antimicrobial peptides in adult flies and leads to reduced host survival following systemic bacterial challenge. Co-immunoprecipitation assays demonstrate a physical interaction between endogenous Mi-2 and Foxo in the Drosophila fat body. Of interest, Foxo silencing phenocopies Mi-2 knockdown, suggesting a functional interdependence between the two factors. Mechanistically, the Mi-2/Foxo functional complex binds to the 5' flanking region of Peptidoglycan recognition protein SC2 (PGRP-SC2), a negative regulator of the immune deficiency (IMD) signaling pathway, to prevent PGRP-SC2 expression. Genetic epistasis experiments support a hierarchical relationship, with PGRP-SC2 acting downstream of Mi-2/Foxo. Collectively, our findings uncover a previously uncharacterized chromatin-based regulatory mechanism whereby Mi-2 collaborates with Foxo to mediate the antibacterial immune response in Drosophila.
Keywords: Mi-2, Foxo, pgrp-sc2, IMD signaling pathway, Antibacterial immune defense, Drosophila melanogaster
Received: 12 Jul 2025; Accepted: 09 Sep 2025.
Copyright: © 2025 Zheng, Ali, 金, Ding, Zhu, Usama, Cai and JI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xianrui Zheng, Fujian Medical University, Fuzhou, China
Shanming JI, Anhui Agricultural University, Hefei, China
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