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- Title
Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of Salmonella Typhimurium by Enhancing Autophagy in Murine Macrophages.
- Authors
Lee, Hyo-Ji; Lee, Sun-Hye; Jeon, Ji-Hui; Kim, Hyo-Jung; Jeong, Eui-Kwon; Kim, Min-Jeong; Jung, Young Mee; Jung, Yu-Jin
- Abstract
The Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative Gram-negative bacterium that causes acute gastroenteritis and food poisoning. S. Typhimurium can survive within macrophages that are able to initiate the innate immune response after recognizing bacteria via various pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs). In this study, we investigated the effects and molecular mechanisms by which agonists of endosomal TLRs—especially TLR3—contribute to controlling S. Typhimurium infection in murine macrophages. Treatment with polyinosinic:polycytidylic acid (poly(I:C))—an agonist of TLR3—significantly suppressed intracellular bacterial growth by promoting intracellular ROS production in S. Typhimurium-infected cells. Pretreatment with diphenyleneiodonium (DPI)—an NADPH oxidase inhibitor—reduced phosphorylated MEK1/2 levels and restored intracellular bacterial growth in poly(I:C)-treated cells during S. Typhimurium infection. Nitric oxide (NO) production increased through the NF-κB-mediated signaling pathway in poly(I:C)-treated cells during S. Typhimurium infection. Intracellular microtubule-associated protein 1A/1B-light chain 3 (LC3) levels were increased in poly(I:C)-treated cells; however, they were decreased in cells pretreated with 3-methyladenine (3-MA)—a commonly used inhibitor of autophagy. These results suggest that poly(I:C) induces autophagy and enhances ROS production via MEK1/2-mediated signaling to suppress intracellular bacterial growth in S. Typhimurium-infected murine macrophages, and that a TLR3 agonist could be developed as an immune enhancer to protect against S. Typhimurium infection.
- Subjects
TYPHOID fever; SALMONELLA typhimurium; TOLL-like receptors; SALMONELLA enterica serovar typhimurium; AUTOPHAGY; MACROPHAGES
- Publication
Metabolites (2218-1989), 2021, Vol 11, Issue 9, p602
- ISSN
2218-1989
- Publication type
Article
- DOI
10.3390/metabo11090602