The Dual NOD1/NOD2 Agonism of Muropeptides Containing a Meso-Diaminopimelic Acid Residue
| Autor: | Mikhail Pashenkov, Biana I. Alkhazova, Vyacheslav L. L’vov, Yulia A. Dagil, Nikolai P. Arbatsky, Dmitriy Mazurov |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Molecular biology Nod2 Signaling Adaptor Protein lcsh:Medicine Peptide Diaminopimelic Acid Biochemistry Monocytes White Blood Cells chemistry.chemical_compound 0302 clinical medicine Animal Cells Nod1 Signaling Adaptor Protein NOD1 Medicine and Health Sciences Small interfering RNAs Enzyme-Linked Immunoassays lcsh:Science Cells Cultured chemistry.chemical_classification Multidisciplinary biology Biological activity Nucleic acids Cytokines Cellular Types Diaminopimelic acid Research Article Gram-negative bacteria Immune Cells Immunology DNA construction Transfection Microbiology 03 medical and health sciences Residue (chemistry) Adjuvants Immunologic Genetics Humans Non-coding RNA Immunoassays Gram Negative Bacteria Blood Cells Innate immune system Macrophages fungi lcsh:R Biology and Life Sciences Bacteriology Cell Biology biology.organism_classification Immunity Innate digestive system diseases Gene regulation Research and analysis methods body regions carbohydrates (lipids) Molecular biology techniques HEK293 Cells 030104 developmental biology chemistry Plasmid Construction Immunologic Techniques RNA lcsh:Q Gene expression Peptidoglycan 030217 neurology & neurosurgery Cloning |
| Zdroj: | PLoS ONE, Vol 11, Iss 8, p e0160784 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Muropeptides are fragments of peptidoglycan that trigger innate immune responses by activating nucleotide-binding oligomerization domain (NOD) 1 and NOD2. Muropeptides from Gram-negative bacteria contain a meso-diaminopimelic acid (meso-DAP) residue in either a terminal or a non-terminal position. While the former ones are known to be recognized by NOD1, much less is known about recognition of muropeptides with non-terminal meso-DAP, which are most abundant moieties of Gram-negative peptidoglycans. Here, we developed a novel system to assess biological activity of muropeptides, based on CRISPR/Cas9-mediated knockout (KO) of NOD1 and NOD2 genes in modified HEK293T cells. Using NOD1/NOD2 knockout and overexpression systems, as well as human monocytes and macrophages, we refine the current view of muropeptide recognition. We show that NOD2 can recognize different natural muropeptides containing a meso-DAP residue (preferably in a non-terminal position), provided they are present at micromolar concentrations. NOD2 accepts muropeptides with long and branched peptide chains and requires an intact N-acetylmuramyl residue. Muropeptides with non-terminal meso-DAP can activate NOD1 as well, but, in this case, probably require peptidase pre-processing to expose the meso-DAP residue. Depending on NOD1/NOD2 ratio in specific cell types, meso-DAP-containing muropeptides can be recognized either primarily via NOD2 (in monocytes) or via NOD1 (in monocyte-derived macrophages and HEK293T-derived cells). The dual NOD1/NOD2 agonism of meso-DAP-containing muropeptides should be taken into account when assessing cellular responses to muropeptides and designing muropeptide immunostimulants and vaccine adjuvants. |
| Databáze: | OpenAIRE |
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