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The oxygen interplay in host-pathogen interactions

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.

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

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.