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

Anne-Laure Roux; Aurélie Ray; Alexandre Pawlik; Halima Medjahed; Gilles Etienne; Martin Rottman; Emilie Catherinot; Jean-Yves Coppée; Karima Chaoui; Bernard Monsarrat; Antoine Toubert; Mamadou Daffé; Germain Puzo; Jean-Louis Gaillard; Roland Brosch; Nicolas Dulphy; Jérôme Nigou; Jean-Louis Herrmann

doi:10.1111/j.1462-5822.2010.01565.x

Journal articles

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

Anne-Laure Roux ^{1, 2} Aurélie Ray ^{3, 4} Alexandre Pawlik ^{5, 1, 2} Halima Medjahed ⁶ Gilles Etienne ^{4, 3} Martin Rottman ^{2, 1} Emilie Catherinot ^{2, 1} Jean-Yves Coppée ⁷ Karima Chaoui ^{3, 4} Bernard Monsarrat ^{3, 4} Antoine Toubert ⁸ Mamadou Daffé ^{3, 4} Germain Puzo ^{3, 4} Jean-Louis Gaillard ^{1, 2} Roland Brosch ⁵ Nicolas Dulphy ⁸ Jérôme Nigou ^{3, 4} Jean-Louis Herrmann ^{9, 1, *}

* Corresponding author

1 EPIM - Epidémiologie et Physiopathologie des Infections Microbiennes

2I - Infection et inflammation

2 Service de Microbiologie [Garches]

3 IPBS - Institut de pharmacologie et de biologie structurale

4 UT3 - Université Toulouse III - Paul Sabatier

5 Pathogénomique mycobactérienne intégrée

6 Inserm U1002 - Pathogénie des infections systémiques

7 PF2 - Transcriptome et Epigénome

8 Service d'Immunologie et d'Histocompatibilité

9 2I - Infection et inflammation

Abstract : 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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Microbiology and Parasitology / Bacteriology

Life Sciences [q-bio] / Human health and pathology / Emerging diseases

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https://hal-pasteur.archives-ouvertes.fr/pasteur-02618829
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Overexpression of proinflammatory TLR-2-signalling lipoproteins in hypervirulent mycobacterial variants

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

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