Loss of NR2F6 Protects from Salmonella Typhimurium Infection
Woelk J, Pfeifhofer-Obermair C, Benz J, Brigo N, Bamberger M, Kleiter A, Hermann M, Weiss G, Hermann-Kleiter N (2025)
Publication Type: Journal article
Publication year: 2025
Journal
Abstract
Nuclear receptors regulate key functions of mononuclear phagocytes and are critical components of the innate immune system, acting as regulators of organ health and disease. In healthy mice, the loss of the nuclear orphan receptor NR2F6 alters tissue-resident macrophage populations in the liver, lung, and spleen. In response to Salmonella Typhimurium infection, Nr2f6-deficient mice exhibit improved clinical outcomes, characterized by reduced weight loss, bacterial loads in the spleen and liver, and decreased plasma pro-inflammatory cytokines. Despite unchanged basal iron metabolism in the spleen and liver, iron regulatory proteins and the interleukin (IL)-6-hepcidin axis are altered in Nr2f6-deficient mice during Salmonella infection, reducing hypoferremia. Transcriptomic analysis of splenic red pulp macrophages reveals significant alterations of phagocytosis-related genes, including upregulation of signal-regulatory protein alpha (Sirpa). In vitro, phagocytosis of red blood cells, regulated by the inhibitory CD47-Sirpα axis, and Salmonella Typhimurium phagocytosis are significantly impaired in Nr2f6-deficient splenic macrophages. Blocking Sirpα in vitro restores the phagocytic activity of Nr2f6-deficient macrophages to wild-type levels. In vivo, Salmonella Typhimurium loads are partially increased post-infection in anti-Sirpα treated Nr2f6-deficient mice. These findings uncover a previously unrecognized role of NR2F6 in host-pathogen interactions, positioning it as a potential therapeutic target for infectious diseases.
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Austria (AT)How to cite
APA:
Woelk, J., Pfeifhofer-Obermair, C., Benz, J., Brigo, N., Bamberger, M., Kleiter, A.,... Hermann-Kleiter, N. (2025). Loss of NR2F6 Protects from Salmonella Typhimurium Infection. Advanced Science. https://doi.org/10.1002/advs.202404280
MLA:
Woelk, Johannes, et al. "Loss of NR2F6 Protects from Salmonella Typhimurium Infection." Advanced Science (2025).
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