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The Network aims to promote multi-disciplinary approaches to address challenging vaccine-related questions. This page contains a curated list of publications that highlight high-impact and collaborative approaches.
@article{Pallett:2017:10.1038/mi.2016.77,
author = {Pallett, MA and Crepin, VF and Serafini, N and Habibzay, M and Kotik, O and Sanchez-Garrido, J and Di, Santo J and Shenoy, AR and Berger, CN and Frankel, GM},
doi = {10.1038/mi.2016.77},
journal = {Mucosal Immunology},
pages = {602--612},
title = {Bacterial virulence factor inhibits caspase-4/11 activation in intestinal epithelial cells},
url = {http://dx.doi.org/10.1038/mi.2016.77},
volume = {10},
year = {2017}
}
TY - JOUR
AB - The human pathogen enteropathogenic Escherichia coli (EPEC), as well as the mouse pathogen Citrobacter rodentium, colonize the gut mucosa via attaching and effacing lesion formation and cause diarrheal diseases. EPEC and C. rodentium type III secretion system (T3SS) effectors repress innate immune responses and infiltration of immune cells. Inflammatory caspases such as caspase-1 and caspase-4/11 are crucial mediators of host defense and inflammation in the gut via their ability to process cytokines such as interleukin (IL)-1β and IL-18. Here we report that the effector NleF binds the catalytic domain of caspase-4 and inhibits its proteolytic activity. Following infection of intestinal epithelial cells (IECs) EPEC inhibited caspase-4 and IL-18 processing in an NleF-dependent manner. Depletion of caspase-4 in IECs prevented the secretion of mature IL-18 in response to infection with EPECΔnleF. NleF-dependent inhibition of caspase-11 in colons of mice prevented IL-18 secretion and neutrophil influx at early stages of C. rodentium infection. Neither wild-type C. rodentium nor C. rodentiumΔnleF triggered neutrophil infiltration or IL-18 secretion in Cas11 or Casp1/11-deficient mice. Thus, IECs have a key role in modulating early innate immune responses in the gut via a caspase-4/11—IL-18 axis, which is targeted by virulence factors encoded by enteric pathogens.
AU - Pallett,MA
AU - Crepin,VF
AU - Serafini,N
AU - Habibzay,M
AU - Kotik,O
AU - Sanchez-Garrido,J
AU - Di,Santo J
AU - Shenoy,AR
AU - Berger,CN
AU - Frankel,GM
DO - 10.1038/mi.2016.77
EP - 612
PY - 2017///
SN - 1935-3456
SP - 602
TI - Bacterial virulence factor inhibits caspase-4/11 activation in intestinal epithelial cells
T2 - Mucosal Immunology
UR - http://dx.doi.org/10.1038/mi.2016.77
UR - http://hdl.handle.net/10044/1/50872
VL - 10
ER -
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