Lipoglycans contribute to innate immune detection of mycobacteria.
Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purifie...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3229593?pdf=render |
| _version_ | 1818442157997948928 |
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| author | Shyam Krishna Aurélie Ray Shiv K Dubey Gérald Larrouy-Maumus Christian Chalut Romain Castanier Audrey Noguera Martine Gilleron Germain Puzo Alain Vercellone K Madhavan Nampoothiri Jérôme Nigou |
| author_facet | Shyam Krishna Aurélie Ray Shiv K Dubey Gérald Larrouy-Maumus Christian Chalut Romain Castanier Audrey Noguera Martine Gilleron Germain Puzo Alain Vercellone K Madhavan Nampoothiri Jérôme Nigou |
| author_sort | Shyam Krishna |
| collection | DOAJ |
| description | Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infection remains unclear. To address this question, we used the model organism Mycobacterium smegmatis to generate mutants altered for the production of lipoglycans. Since their biosynthesis cannot be fully abrogated, we manipulated the biosynthesis pathway of GDP-Mannose to obtain some strains with either augmented (∼1.7 fold) or reduced (∼2 fold) production of lipoglycans. Interestingly, infection experiments demonstrated a direct correlation between the amount of lipoglycans in the bacterial cell envelope on one hand and the magnitude of innate immune signaling in TLR2 reporter cells, monocyte/macrophage THP-1 cell line and human dendritic cells, as revealed by NF-κB activation and IL-8 production, on the other hand. These data establish that lipoglycans are bona fide Microbe-Associated Molecular Patterns contributing to innate immune detection of mycobacteria, via TLR2 among other PRRs. |
| first_indexed | 2024-12-14T18:39:41Z |
| format | Article |
| id | doaj.art-75d5daaf5db34bbf9867ee00db3b4976 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T18:39:41Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-75d5daaf5db34bbf9867ee00db3b49762022-12-21T22:51:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2847610.1371/journal.pone.0028476Lipoglycans contribute to innate immune detection of mycobacteria.Shyam KrishnaAurélie RayShiv K DubeyGérald Larrouy-MaumusChristian ChalutRomain CastanierAudrey NogueraMartine GilleronGermain PuzoAlain VercelloneK Madhavan NampoothiriJérôme NigouInnate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infection remains unclear. To address this question, we used the model organism Mycobacterium smegmatis to generate mutants altered for the production of lipoglycans. Since their biosynthesis cannot be fully abrogated, we manipulated the biosynthesis pathway of GDP-Mannose to obtain some strains with either augmented (∼1.7 fold) or reduced (∼2 fold) production of lipoglycans. Interestingly, infection experiments demonstrated a direct correlation between the amount of lipoglycans in the bacterial cell envelope on one hand and the magnitude of innate immune signaling in TLR2 reporter cells, monocyte/macrophage THP-1 cell line and human dendritic cells, as revealed by NF-κB activation and IL-8 production, on the other hand. These data establish that lipoglycans are bona fide Microbe-Associated Molecular Patterns contributing to innate immune detection of mycobacteria, via TLR2 among other PRRs.http://europepmc.org/articles/PMC3229593?pdf=render |
| spellingShingle | Shyam Krishna Aurélie Ray Shiv K Dubey Gérald Larrouy-Maumus Christian Chalut Romain Castanier Audrey Noguera Martine Gilleron Germain Puzo Alain Vercellone K Madhavan Nampoothiri Jérôme Nigou Lipoglycans contribute to innate immune detection of mycobacteria. PLoS ONE |
| title | Lipoglycans contribute to innate immune detection of mycobacteria. |
| title_full | Lipoglycans contribute to innate immune detection of mycobacteria. |
| title_fullStr | Lipoglycans contribute to innate immune detection of mycobacteria. |
| title_full_unstemmed | Lipoglycans contribute to innate immune detection of mycobacteria. |
| title_short | Lipoglycans contribute to innate immune detection of mycobacteria. |
| title_sort | lipoglycans contribute to innate immune detection of mycobacteria |
| url | http://europepmc.org/articles/PMC3229593?pdf=render |
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