Overexpression of proinflammatory TLR-2-signalling lipoproteins in hypervirulent mycobacterial variants

EA 3647 Physiopathologie et diagnostic des infections microbiennes, Université Versailles St Quentin, and Laboratoire de Microbiologie, Hôpital Raymond Poincaré, AP-HP, Garches, France.
Cellular Microbiology (Impact Factor: 4.92). 12/2010; 13(5):692-704. DOI: 10.1111/j.1462-5822.2010.01565.x
Source: PubMed


Changes in the cell envelope composition of mycobacteria cause major changes in cytokine profiles of infected antigen presenting cells. We describe here the modulation of inflammatory responses by Mycobacterium abscessus, an emerging pathogen in cystic fibrosis. M. abscessus is able to switch from a smooth (S) to a rough (R) morphotype by the loss of a surface glycopeptidolipid. R variants are associated with severe clinical forms and a 'hyper-proinflammatory' response in ex vivo and in vivo models. Using partitioning of cell surface components we found that a complex fraction, more abundant in R variants than in S variants, made a major contribution to the TLR-2-dependent hyper-proinflammatory response induced by R variants. Lipoproteins were the main TLR-2 agonists in this fraction, consistent with the larger amounts of 16 lipoproteins in cell surface extracts from R variants; 15 out of 16 being more strongly induced in R variant than in S variant. Genetic interruption of glycopeptidolipid pathway in wild-type S variant resulted in R phenotype with similar induction of lipoprotein genes. In conclusion, R morphotype in M. abscessus is associated with increased synthesis/exposure at the cell surface of lipoproteins, these changes profoundly modifying the innate immune response through TLR-2-dependent mechanisms.

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Available from: Nicolas Dulphy, Oct 06, 2014
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    • "Previous studies showed that Mabc R variants were associated with TLR2-dependent hyper-proinflammatory responses via increased synthesis/exposure at the cell surface of lipoproteins [29]. However, the association between bacterial colony morphotypes and innate immune responses in Mmass infection has not been characterized. "
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