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Bacterial inhibition of CD8 + T-cells mediated cell death promotes neuroinvasion and within-host persistence

Abstract : Abstract Central nervous system infections are amongst the most severe 1,2 , yet the mechanisms by which pathogens access the brain remain poorly understood. The model microorganism Listeria monocytogenes (Lm) is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest central nervous system infections 3,4 . While immunosuppression is a well-established host risk factor for neurolisteriosis 3,5 , little is known regarding the bacterial factors underlying Lm neuroinvasion. We have developed a clinically-relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains 6 inoculated in a humanized mouse model of infection 7 , and we show that the bacterial protein InlB protects infected monocytes from CD8 + T-cells Fas-mediated cell death, in a c-Met/PI3-kinase/FLIP-dependent manner. This blockade of anti- Lm specific cellular immune response lengthens infected monocytes lifespan, favoring Lm transfer from infected monocytes to the brain. The intracellular niche created by InlB-mediated cell-autonomous immunosuppression also promotes Lm fecal shedding, accounting for its selection as a Lm core virulence gene. Here, we have uncovered an unanticipated specific mechanism by which a bacterial pathogen confers to the cells it infects an increased lifespan by rendering them resistant to cell-mediated immunity. This promotes Lm within-host persistence and dissemination to the central nervous system, and transmission.
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Submitted on : Friday, June 25, 2021 - 5:03:48 PM
Last modification on : Thursday, April 7, 2022 - 1:58:13 PM
Long-term archiving on: : Sunday, September 26, 2021 - 10:29:33 PM


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Claire Maudet, Marouane Kheloufi, Sylvain Levallois, Julien Gaillard, Lei Huang, et al.. Bacterial inhibition of CD8 + T-cells mediated cell death promotes neuroinvasion and within-host persistence. 2021. ⟨pasteur-03271418⟩



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