HAL will be down for maintenance from Friday, June 10 at 4pm through Monday, June 13 at 9am. More information
Skip to Main content Skip to Navigation
Preprints, Working Papers, ...

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.
Complete list of metadata

https://hal-pasteur.archives-ouvertes.fr/pasteur-03271418
Contributor : Andrée Diakite Connect in order to contact the contributor
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

File

2020.11.20.384974v1.full.pdf
Files produced by the author(s)

Licence

Copyright

Identifiers

Collections

Citation

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⟩

Share

Metrics

Record views

27

Files downloads

13