Neubert, Patrick and Weichselbaum, Andrea and Reitinger, Carmen and Schatz, Valentin and Schroeder, Agnes and Ferdinand, John R. and Simon, Michaela and Baer, Anna-Lorena and Brochhausen, Christoph and Gerlach, Roman G. and Tomiuk, Stefan and Hammer, Karin and Wagner, Stefan and van Zandbergen, Ger and Binger, Katrina J. and Mueller, Dominik N. and Kitada, Kento and Clatworthy, Menna R. and Kurts, Christian and Titze, Jens and Abdullah, Zeinab and Jantsch, Jonathan (2019) HIF1A and NFAT5 coordinate Na+-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting. AUTOPHAGY, 15 (11). pp. 1899-1916. ISSN 1554-8627, 1554-8635
Full text not available from this repository. (Request a copy)Abstract
Infection and inflammation are able to induce diet-independent Na+-accumulation without commensurate water retention in afflicted tissues, which favors the pro-inflammatory activation of mouse macrophages and augments their antibacterial and antiparasitic activity. While Na+-boosted host defense against the protozoan parasite Leishmania major is mediated by increased expression of the leishmanicidal NOS2 (nitric oxide synthase 2, inducible), the molecular mechanisms underpinning this enhanced antibacterial defense of mouse macrophages with high Na+ (HS) exposure are unknown. Here, we provide evidence that HS-increased antibacterial activity against E. coli was neither dependent on NOS2 nor on the phagocyte oxidase. In contrast, HS-augmented antibacterial defense hinged on HIF1A (hypoxia inducible factor 1, alpha subunit)-dependent increased autophagy, and NFAT5 (nuclear factor of activated T cells 5)-dependent targeting of intracellular E. coli to acidic autolysosomal compartments. Overall, these findings suggest that the autolysosomal compartment is a novel target of Na+-modulated cell autonomous innate immunity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HYPOXIA-INDUCIBLE FACTOR; MAMMALIAN TARGET; GENE-EXPRESSION; MACROPHAGES; INDUCTION; PROTEIN; ACTIVATION; TRANSCRIPTION; ALPHA; REPLICATION; Autophagy; cell-autonomous immunity; E. coli; macrophage; salt; sodium |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Medicine > Lehrstuhl für Kieferorthopädie Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Apr 2020 06:03 |
| Last Modified: | 14 Apr 2020 06:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27164 |
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