Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of <i>Salmonella</i> Typhimurium by Enhancing Autophagy in Murine Macrophages
The <i>Salmonella enterica</i> serovar Typhimurium (<i>S.</i> Typhimurium) is a facultative Gram-negative bacterium that causes acute gastroenteritis and food poisoning. <i>S</i>. Typhimurium can survive within macrophages that are able to initiate the innate immu...
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2021-09-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/9/602 |
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| author | Hyo-Ji Lee Sun-Hye Lee Ji-Hui Jeon Hyo-Jung Kim Eui-Kwon Jeong Min-Jeong Kim Young Mee Jung Yu-Jin Jung |
| author_facet | Hyo-Ji Lee Sun-Hye Lee Ji-Hui Jeon Hyo-Jung Kim Eui-Kwon Jeong Min-Jeong Kim Young Mee Jung Yu-Jin Jung |
| author_sort | Hyo-Ji Lee |
| collection | DOAJ |
| description | The <i>Salmonella enterica</i> serovar Typhimurium (<i>S.</i> Typhimurium) is a facultative Gram-negative bacterium that causes acute gastroenteritis and food poisoning. <i>S</i>. 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 <i>S</i>. 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 <i>S</i>. 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 <i>S</i>. Typhimurium infection. Nitric oxide (NO) production increased through the NF-κB-mediated signaling pathway in poly(I:C)-treated cells during <i>S</i>. 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 <i>S</i>. Typhimurium-infected murine macrophages, and that a TLR3 agonist could be developed as an immune enhancer to protect against <i>S</i>. Typhimurium infection. |
| first_indexed | 2024-03-10T07:27:10Z |
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| id | doaj.art-917c502fe5604e7fb584d66333ca6eba |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T07:27:10Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-917c502fe5604e7fb584d66333ca6eba2023-11-22T14:11:35ZengMDPI AGMetabolites2218-19892021-09-0111960210.3390/metabo11090602Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of <i>Salmonella</i> Typhimurium by Enhancing Autophagy in Murine MacrophagesHyo-Ji Lee0Sun-Hye Lee1Ji-Hui Jeon2Hyo-Jung Kim3Eui-Kwon Jeong4Min-Jeong Kim5Young Mee Jung6Yu-Jin Jung7Department of Biological Sciences, Kangwon National University, Chuncheon 24341, KoreaBIT Medical Convergence Graduate Program, Kangwon National University, Chuncheon 24341, KoreaDepartment of Biological Sciences, Kangwon National University, Chuncheon 24341, KoreaBIT Medical Convergence Graduate Program, Kangwon National University, Chuncheon 24341, KoreaBIT Medical Convergence Graduate Program, Kangwon National University, Chuncheon 24341, KoreaBIT Medical Convergence Graduate Program, Kangwon National University, Chuncheon 24341, KoreaKangwon Radiation Convergence Research Support Center, Kangwon National University, Chuncheon 24341, KoreaDepartment of Biological Sciences, Kangwon National University, Chuncheon 24341, KoreaThe <i>Salmonella enterica</i> serovar Typhimurium (<i>S.</i> Typhimurium) is a facultative Gram-negative bacterium that causes acute gastroenteritis and food poisoning. <i>S</i>. 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 <i>S</i>. 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 <i>S</i>. 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 <i>S</i>. Typhimurium infection. Nitric oxide (NO) production increased through the NF-κB-mediated signaling pathway in poly(I:C)-treated cells during <i>S</i>. 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 <i>S</i>. Typhimurium-infected murine macrophages, and that a TLR3 agonist could be developed as an immune enhancer to protect against <i>S</i>. Typhimurium infection.https://www.mdpi.com/2218-1989/11/9/602autophagymacrophagereactive oxygen species (ROS)<i>Salmonella enterica</i> serovar TyphimuriumToll-like receptor 3 |
| spellingShingle | Hyo-Ji Lee Sun-Hye Lee Ji-Hui Jeon Hyo-Jung Kim Eui-Kwon Jeong Min-Jeong Kim Young Mee Jung Yu-Jin Jung Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of <i>Salmonella</i> Typhimurium by Enhancing Autophagy in Murine Macrophages Metabolites autophagy macrophage reactive oxygen species (ROS) <i>Salmonella enterica</i> serovar Typhimurium Toll-like receptor 3 |
| title | Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of <i>Salmonella</i> Typhimurium by Enhancing Autophagy in Murine Macrophages |
| title_full | Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of <i>Salmonella</i> Typhimurium by Enhancing Autophagy in Murine Macrophages |
| title_fullStr | Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of <i>Salmonella</i> Typhimurium by Enhancing Autophagy in Murine Macrophages |
| title_full_unstemmed | Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of <i>Salmonella</i> Typhimurium by Enhancing Autophagy in Murine Macrophages |
| title_short | Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of <i>Salmonella</i> Typhimurium by Enhancing Autophagy in Murine Macrophages |
| title_sort | stimulation of toll like receptor 3 diminishes intracellular growth of i salmonella i typhimurium by enhancing autophagy in murine macrophages |
| topic | autophagy macrophage reactive oxygen species (ROS) <i>Salmonella enterica</i> serovar Typhimurium Toll-like receptor 3 |
| url | https://www.mdpi.com/2218-1989/11/9/602 |
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