Bacterial Peptidoglycan Fragments Differentially Regulate Innate Immune Signaling
| العنوان: | Bacterial Peptidoglycan Fragments Differentially Regulate Innate Immune Signaling |
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| المؤلفون: | Rachid Zagani, Siavash Mashayekh, Shuzhen Liu, Hans Christian Reinecker, Catherine L. Grimes, Klare L. Bersch, Kimberly A. Wodzanowski, Kristen E. DeMeester, Shuyuan Chen |
| المصدر: | ACS Central Science, Vol 7, Iss 4, Pp 688-696 (2021) ACS Central Science |
| بيانات النشر: | American Chemical Society, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Innate immune system, 010405 organic chemistry, General Chemical Engineering, Pattern recognition receptor, Disaccharide, General Chemistry, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Proinflammatory cytokine, Cell biology, chemistry.chemical_compound, Chemistry, chemistry, Microbiome, Peptidoglycan, Receptor, QD1-999, Muramyl dipeptide, Research Article |
| الوصف: | The human innate immune system responds to both pathogen and commensal bacteria at the molecular level using bacterial peptidoglycan (PG) recognition elements. Traditionally, synthetic and commercially accessible PG monosaccharide units known as muramyl dipeptide (MDP) and N-glycolyl MDP (ng-MDP) have been used to probe the mechanism of innate immune activation of pattern recognition receptors, such as NOD-like receptors. However, bacterial PG is a dynamic and complex structure, with various chemical modifications and trimming mechanisms that result in the production of disaccharide-containing elements. These molecules pose as attractive targets for immunostimulatory screening; however, studies are limited because of their synthetic accessibility. Inspired by disaccharide-containing compounds produced from the gut microbe Lactobacillus acidophilus, a robust and scalable chemical synthesis of PG-based disaccharide ligands was implemented. Together with a monosaccharide PG library, compounds were screened for their ability to stimulate proinflammatory genes in bone-marrow-derived macrophages. The data reveal distinct gene induction patterns for monosaccharide and disaccharide PG units, suggesting that PG innate immune signaling is more complex than a one activator–one pathway program, as biologically relevant fragments induce transcriptional programs to different degrees. These disaccharide molecules will serve as critical immunostimulatory tools to more precisely define specialized innate immune regulatory mechanisms that distinguish between commensal and pathogenic bacteria residing in the microbiome. Synthesis of biologically inspired peptidoglycan fragments reveals a complex immune pathway activating transcriptional programs that induce genes associated with inflammatory bowel disease. |
| اللغة: | English |
| تدمد: | 2374-7951 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::80f04a52ded8a9bf31d613409f8f4ca4 https://doaj.org/article/1c648835b7ca46ac9d60b777f89121f5 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....80f04a52ded8a9bf31d613409f8f4ca4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23747951 |
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