Dataset Information

Transcytosis subversion by M cell-to-enterocyte spread promotes Shigella flexneri and Listeria monocytogenes intracellular bacterial dissemination.

ABSTRACT: Microfold (M) cell host-pathogen interaction studies would benefit from the visual analysis of dynamic cellular and microbial interplays. We adapted a human in vitro M cell model to physiological bacterial infections, expression of fluorescent localization reporters and long-term three-dimensional time-lapse microscopy. This approach allows following key steps of M cell infection dynamics at subcellular resolution, from the apical onset to basolateral epithelial dissemination. We focused on the intracellular pathogen Shigella flexneri, classically reported to transcytose through M cells to initiate bacillary dysentery in humans, while eliciting poorly protective immune responses. Our workflow was critical to reveal that S. flexneri develops a bimodal lifestyle within M cells leading to rapid transcytosis or delayed vacuolar rupture, followed by direct actin motility-based propagation to neighboring enterocytes. Moreover, we show that Listeria monocytogenes, another intracellular pathogen sharing a tropism for M cells, disseminates in a similar manner and evades M cell transcytosis completely. We established that actin-based M cell-to-enterocyte spread is the major dissemination pathway for both pathogens and avoids their exposure to basolateral compartments in our system. Our results challenge the notion that intracellular pathogens are readily transcytosed by M cells to inductive immune compartments in vivo, providing a potential mechanism for their ability to evade adaptive immunity.

SUBMITTER: Rey C

PROVIDER: S-EPMC7179946 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transcytosis subversion by M cell-to-enterocyte spread promotes Shigella flexneri and Listeria monocytogenes intracellular bacterial dissemination.

Rey Camille C Chang Yuen-Yan YY Latour-Lambert Patricia P Varet Hugo H Proux Caroline C Legendre Rachel R Coppée Jean-Yves JY Enninga Jost J

PLoS pathogens 20200413 4

Microfold (M) cell host-pathogen interaction studies would benefit from the visual analysis of dynamic cellular and microbial interplays. We adapted a human in vitro M cell model to physiological bacterial infections, expression of fluorescent localization reporters and long-term three-dimensional time-lapse microscopy. This approach allows following key steps of M cell infection dynamics at subcellular resolution, from the apical onset to basolateral epithelial dissemination. We focused on the ...[more]

PMID: 32282860

Similar Datasets

Project description:For many intracellular pathogens, their virulence depends on an ability to spread between cells of an epithelial layer. For intercellular spread to occur, these pathogens deform the plasma membrane into a protrusion structure that is engulfed by the neighboring cell. Although the polymerization of actin is essential for spread, how these pathogens manipulate the actin cytoskeleton in a manner that enables protrusion formation is still incompletely understood. Here, we identify the mammalian actin binding protein synaptopodin as required for efficient intercellular spread. Using a model cytosolic pathogen, Shigella flexneri, we show that synaptopodin increases actin recruitment around bacteria and stabilizes the position of the actin tail at the posterior pole of the bacteria. We show that synaptopodin presence enables protrusions to form and to resolve at a greater rate, indicating that the proper alignment of the tail enables the bacteria to push against the membrane with greater force. We demonstrate that synaptopodin recruitment around bacteria requires the bacterial protein IcsA, and we show that this recruitment is further enhanced in a type 3 secretion system dependent manner. Myosin X, known to enhance protrusion formation, is associated with more intracellular bacteria in the presence of synaptopodin. These data establish synaptopodin as required for intracellular bacteria to reprogram the actin cytoskeleton in a manner that enables efficient protrusion formation and enhance our understanding of the cellular function of synaptopodin.SignificanceIntercellular spread is essential for many cytosolic dwelling pathogens during their infectious life cycle. Despite knowing the steps required for intercellular spread, relatively little is known about the host-pathogen interactions that enable these steps to occur. Here, we identify a requirement for the actin binding protein synaptopodin during intercellular spread by cytosolic bacteria. We show synaptopodin is necessary for the organization and abundance of actin around bacteria. We also demonstrate synaptopodin is necessary for the formation of plasma membrane structures known as protrusions that are necessary for the movement of these bacteria between cells. Thus, these findings implicate synaptopodin as an important actin-binding protein for the virulence of intracellular pathogens that require the actin cytoskeleton and spread between cells.

Dataset Information

Transcytosis subversion by M cell-to-enterocyte spread promotes Shigella flexneri and Listeria monocytogenes intracellular bacterial dissemination.

Publications

Transcytosis subversion by M cell-to-enterocyte spread promotes Shigella flexneri and Listeria monocytogenes intracellular bacterial dissemination.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets