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Pathogenèse des infections bactériennes et immunité - B. Marteyn

Headed by Dr Benoit Marteyn (Inserm Director, DR)

2-year Postdoctoral fellowshipat IBMC CNRS / University of Strasbourg, France in our Team “Pathogenesis of Bacterial Infections and Immunity.

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The oxygen interplay in host-pathogen interactions

Our team works at the interface of microbiology, immunology and cell biology. We aim at deciphering the role of oxygen in host-pathogen interactions, using the enteropathogen Shigella flexneri as a model and focusing on the neutrophil-mediated immune response. This question will be address at the different steps of the infectious process from epithelial cell invasion to the formation of foci of infection and to the dissemination within tissues.

Shigella forms hypoxic foci of infection within the colonic mucosa. Guinea pig model of infection (Shigella:green, hypoxia:red, neutrophils:blue , with Myelotracker-Alexa405)

We previously demonstrated that Shigella flexneri invasion capacity in vivo (mediated by the T3SS) relies on the presence of oxygen, which diffuses at the tip of intestinal villi, within the mucus layer (Marteyn et al. 2010). In another hand, we observed that hypoxia is induced during Shigella flexneri infectious foci formation (Arena et al. 2016). We identified Shigella flexneri aerobic respiration as the main trigger of oxygen depletion in host tissues (Tinevez et al, in revision at Nat. Micro.), hence elucidating the molecular mechanisms of the infectious hypoxia induction.

Taken together, these results strongly suggest that the interaction between Shigella flexneri and immune cells, including neutrophils, recruited at foci of infection occurs under various oxygen levels and mainly under low-oxygen conditions.

In this context, we develop innovative tools and strategies to decipher (1) the oxygen-dependent modulation of neutrophil survival, (2) the neutrophil antimicrobial functions in hypoxic infectious environments and (3) the activation of Shigella flexneri secretion systems (T3SS and T5SS) in vivo, in regards with oxygen availability. Our ultimate goals are to unravel novel bacteria virulence strategies and immune response adaptation under low-oxygen conditions encountered in vivo. In a translational research perspective, we ambition to identify new targets for the development of efficient vaccine candidates or antimicrobial compounds.

Myelotracker : a new neutrophil marker

Our team as validated a new neutrophil marker, the Myelotracker (MUB40), which specifically binds to neutrophil lactoferrin, stored in granules. Myelotracker may be used to label neutrophils in fixed preparation and to assess the neutrophil degranulation process by live microscopy.

For more informations, go to the Myelotracker webpage

Main publications

- Tinevez JY, Arena ET, Anderson M, Nigro G, Injarabian L, André A, Ferrari M, Campbell-Valois FX, Devin A, Shorte SL, Sansonetti PJ, Marteyn BS. Shigella-mediated oxygen depletion is essential for intestinal mucosa colonization. */Nat Microbiol./* 2019 Aug 5. doi : 10.1038/s41564-019-0525-3.
- Anderson MC, Chaze T, Coïc YM, Injarabian L, Jonsson F, Lombion N, Selimoglu-Buet D, Souphron J, Ridley C, Vonaesch P, Baron B, Arena ET, Tinevez JY, Nigro G,Nothelfer K, Solary E, Lapierre V, Lazure T, Matondo M, Thornton D,Sansonetti PJ, Baleux F, Marteyn BS. MUB40 Binds to Lactoferrin and Stands as a Specific Neutrophil Marker. */Cell Chem Biol/*. 2018 Apr 19 ; 25(4):483-493
- Anderson MC, Vonaesch P, Saffarian A, Marteyn BS, Sansonetti PJ. Shigella sonnei Encodes a Functional T6SS Used for Interbacterial Competition and Niche Occupancy. */Cell Host Microbe/*. 2017 Jun 14 ; 21(6):769-776
- Arena ET, Tinevez JY, Nigro G, Sansonetti PJ, Marteyn BS. The infectious hypoxia : occurrence and causes during Shigella infection. /Microbes Infect./ 2017 Mar ; 19(3):157-165.
- Monceaux V, Chiche-Lapierre C, Chaput C, Witko-Sarsat V, Prevost MC, Taylor CT, Ungeheuer MN, Sansonetti PJ, Marteyn BS. Anoxia and glucose supplementation preserve neutrophil viability and function. */Blood/*. 2016 Aug 18 ; 128(7):993-1002
- Marteyn BS, Karimova G, Fenton AK, Gazi AD, West N, Touqui L, Prevost MC, Betton JM, Poyraz O, Ladant D, Gerdes K, Sansonetti PJ, Tang CM. ZapE is a novelcell division protein interacting with FtsZ and modulating the Z-ring dynamics. */MBio/*. 2014 Mar 4 ; 5(2)
- Marteyn B, West NP, Browning DF, Cole JA, Shaw JG, Palm F, Mounier J, Prévost MC, Sansonetti P, Tang CM. Modulation of Shigella virulence in response to available oxygen in vivo. */Nature/*. 2010 May 20 ; 465(7296):355-8.

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Tel: +33 (0)3 88 41 7083