@article{Deng2026, 
author = {Zihao Deng and Jiazhen Luo and Yufu Zhang and Chen Li and Shixin Deng and Jiazhi He and Zihao He and Wenqi Wu and Renjie Jiao and Jiyong Liu},
title = {PGRP-SC–mediated innate immune memory against pathogenic bacteria in Drosophila},
year = {2026},
journal = {hLife},
volume = {4},
number = {1},
pages = {41-55},
keywords = {innate immune memory, trained immunity, Drosophila melanogaster, peptidoglycan recognition protein SC (PGRP-SC), gut, histone H3 lysine 9 trimethylation (H3K9me3)},
url = {https://www.sciopen.com/article/10.1016/j.hlife.2025.09.003},
doi = {10.1016/j.hlife.2025.09.003},
abstract = {Trained immunity is essential for innate immune cells to retain a memory of previously encountered pathogens, strengthening the hosts’ response against these pathogens. However, the mechanisms governing trained immunity have not been well elucidated. In this study, flies of different genotypes were trained with heat-killed gram-negative (G−) bacteria and subsequently reinfected with live pathogens. The innate immune responses against reinfection were evaluated through assessments of survival rates, antimicrobial peptide expression levels, and bacterial loads, complemented by transcriptomic and chromatin immunoprecipitation (ChIP) analyses. We found that flies trained with heat-killed gram-negative bacteria exhibited a higher survival rate upon secondary infection compared to unprimed flies, which was associated with increased expression of antimicrobial peptides. Priming with G− bacteria increased the sensitivity of the immune deficiency pathway to a second bacterial infection owing to lower levels of peptidoglycan recognition protein SC (PGRP-SC) after the first infection. The gut was the major tissue involved in the downregulation of PGRP-SC expression. The histone H3 lysine 9 trimethylation (H3K9me3) levels were higher at the PGRP-SC loci in immune-trained flies compared to untrained flies, contributing to the suppression of PGRP-SC expression. PGRP-SC overexpression in the fly gut abolished the effect of trained immunity. Taken together, our studies identify an innate immune memory in Drosophila that is regulated by gut-derived PGRP-SC through H3K9me3-mediated epigenetic repression of the PGRP-SC.}
}