Dissecting the immunopathogenesis of Mycobacterium abscessus infection in zebrafish embryos
Event details
| Date | 12.12.2017 |
| Hour | 12:15 |
| Speaker | Laurent Kremer, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, France |
| Location | |
| Category | Conferences - Seminars |
Mycobacterium abscessus is a rapidly growing, nontuberculous, multidrug resistant mycobacterium, which can cause severe lung infections. This mycobacterium, like other mycobacteria, has a lipid-rich hydrophobic cell wall containing unique lipids, of which glycopeptidolipids (GPL) have emerged in recent years as major immunomodulators. M. abscessus presents smooth (S) and rough (R) morphotypes and the difference is determined by the presence or absence, respectively, of GPL. Epidemiological studies suggested that the R variant is involved in more severe clinical forms, with a hyper-proinflammatory response. However, the underlying physiopathological mechanisms remain largely unknown. A zebrafish embryo model was developed to investigate the pathogenesis of M. abscessus infection. In contrast to the S variant, the R variant induces a more robust and lethal infection in embryos, characterized by the formation of extracellular cords and abscesses, often found in the Central Nervous System. The high propensity of M. abscessus R to form cords in vivo prevents the bacilli from being phagocytosed by macrophages and neutrophils and promotes the induction of a strong inflammatory response that leads to rapid tissue damage and to larval death. We conducted a comparative stepwise dissection of the inflammatory response in S and R pathogenesis. Our results highlight the importance of both macrophages and neutrophils in controlling cord formation and production/maintenance of protective granulomas. Moreover, this experimental model emphasizes the requirement of a functional CFTR protein in innate immunity and resistance to M. abscessus infection, which is particularly relevant to infections in cystic fibrosis patients who are vulnerable to M. abscessus infections.
References:
A. Bernut, M. Nguyen-Chi, I. Halloum, J.L. Herrmann, G. Lutfalla, and L. Kremer. 2016. Mycobacterium abscessus-induced granuloma formation is strictly dependent on TNF signaling and neutrophil trafficking. PLOS Pathog. 12: e1005986.
I. Halloum, S. Carrère-Kremer, M. Blaise, A. Viljoen, A. Bernut, V. Le Moigne, C. Vilchèze, Y. Guérardel, G. Lutfalla, J.L. Herrmann, W.R. Jacobs, Jr., and L. Kremer. 2016. Deletion of a dehydratase important for intracellular growth and cording renders rough Mycobacterium abscessus avirulent. Proc. Natl. Acad. Sci USA. 113: E4228-4237.
A. Bernut, J.L. Herrmann, K. Kissa, J.F Dubremetz, J.L. Gaillard, G. Lutfalla, and L. Kremer. 2014. Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation. Proc. Natl. Acad. Sci USA. 111: E943-952.
References:
A. Bernut, M. Nguyen-Chi, I. Halloum, J.L. Herrmann, G. Lutfalla, and L. Kremer. 2016. Mycobacterium abscessus-induced granuloma formation is strictly dependent on TNF signaling and neutrophil trafficking. PLOS Pathog. 12: e1005986.
I. Halloum, S. Carrère-Kremer, M. Blaise, A. Viljoen, A. Bernut, V. Le Moigne, C. Vilchèze, Y. Guérardel, G. Lutfalla, J.L. Herrmann, W.R. Jacobs, Jr., and L. Kremer. 2016. Deletion of a dehydratase important for intracellular growth and cording renders rough Mycobacterium abscessus avirulent. Proc. Natl. Acad. Sci USA. 113: E4228-4237.
A. Bernut, J.L. Herrmann, K. Kissa, J.F Dubremetz, J.L. Gaillard, G. Lutfalla, and L. Kremer. 2014. Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation. Proc. Natl. Acad. Sci USA. 111: E943-952.
Practical information
- Informed public
- Free
Organizer
- Raphael Sommer (Cole lab)