USF2 deficiency enhances intracellular clearance of Salmonella Typhimurium via xenophagy and LC3-associated phagocytosis.
- 1Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic of Korea.
- 2Research Institute of Women's Health, Sookmyung Women's University, Seoul, Republic of Korea.
- 3Creative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, Seoul, South Korea.
Abstract
The upstream stimulatory factor 2 (USF2) is a transcription factor known as a transcriptional activator that binds to E-box motifs in gene promoters. Recently, we reported that USF2 is also a transcriptional repressor of the genes that encode lysosomes and autophagy machinery, and that its deficiency results in the elevation of autophagy. The present study was designed to determine whether the absence of USF2 is responsible for more effective protection of the host cells from bacterial infection and intracellular bacterial growth. In this context, we employed Salmonella enterica serovar Typhimurium (S. Typhimurium) as a model pathogen and monitored the changes in intracellular bacterial burden observed in the wild-type (WT) cells and USF2-deficient cells over the time course of infection. The number of intracellular bacteria increased after infection in WT cells but remained similar or decreased in USF2-deficient cells. This phenomenon was observed in various cell types, including mouse embryonic fibroblasts (MEFs), RAW264.7 macrophage-like cells, and primary bone marrow-derived macrophages (BMDMs). The phagocytosis levels were the same in WT and USF2-deficient macrophages, but the latter had a higher basal autophagy, increased lysosome abundance, and increased expression of lysosomal genes. In addition, the components of LC3-associated phagocytosis (LAP), such as LC3B and RUBICON, together with reactive oxygen species (ROS) production, were elevated in USF2-deficient macrophages. Our results demonstrated that the enhanced autophagy in non-phagocytic cells and the elevated autophagy and LAP in phagocytes both contribute to the improved clearance of intracellular pathogens in USF2-deficient cells.
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BibTeX
@article{kwon2026usf2,
title = {{USF2 deficiency enhances intracellular clearance of Salmonella Typhimurium via xenophagy and LC3-associated phagocytosis.}},
author = {Junhee Kwon and Jina Jeon and Ji Won Kim and Hamin Bae and Jaebeom Kim and Young Suk Yu and Sung Hee Baek and Keun Il Kim},
journal = {Animal cells and systems},
year = {2026},
month = oct,
doi = {10.1080/19768354.2026.2721740},
url = {https://europepmc.org/article/MED/42953696},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - USF2 deficiency enhances intracellular clearance of Salmonella Typhimurium via xenophagy and LC3-associated phagocytosis.
AU - Junhee Kwon
AU - Jina Jeon
AU - Ji Won Kim
AU - Hamin Bae
AU - Jaebeom Kim
AU - Young Suk Yu
AU - Sung Hee Baek
AU - Keun Il Kim
PY - 2026
DA - 2026/10/21
JO - Animal cells and systems
DO - 10.1080/19768354.2026.2721740
UR - https://europepmc.org/article/MED/42953696
AB - The upstream stimulatory factor 2 (USF2) is a transcription factor known as a transcriptional activator that binds to E-box motifs in gene promoters. Recently, we reported that USF2 is also a transcriptional repressor of the genes that encode lysosomes and autophagy machinery, and that its deficiency results in the elevation of autophagy. The present study was designed to determine whether the absence of USF2 is responsible for more effective protection of the host cells from bacterial infection and intracellular bacterial growth. In this context, we employed Salmonella enterica serovar Typhimurium (S. Typhimurium) as a model pathogen and monitored the changes in intracellular bacterial burden observed in the wild-type (WT) cells and USF2-deficient cells over the time course of infection. The number of intracellular bacteria increased after infection in WT cells but remained similar or decreased in USF2-deficient cells. This phenomenon was observed in various cell types, including mouse embryonic fibroblasts (MEFs), RAW264.7 macrophage-like cells, and primary bone marrow-derived macrophages (BMDMs). The phagocytosis levels were the same in WT and USF2-deficient macrophages, but the latter had a higher basal autophagy, increased lysosome abundance, and increased expression of lysosomal genes. In addition, the components of LC3-associated phagocytosis (LAP), such as LC3B and RUBICON, together with reactive oxygen species (ROS) production, were elevated in USF2-deficient macrophages. Our results demonstrated that the enhanced autophagy in non-phagocytic cells and the elevated autophagy and LAP in phagocytes both contribute to the improved clearance of intracellular pathogens in USF2-deficient cells.
SN - 1976-8354
SN - 2151-2485
ER -