Imperial College London
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Avinash R. Shenoy

Faculty of Medicine, Department of Infectious Disease

Reader in Innate Immunity and Infection
 
 
 
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Contact

 

+44 (0)20 7594 3785a.shenoy Website

 
 
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Location

 

4.40AFlowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Fisch:2020:10.1016/j.celrep.2020.108008,
author = {Fisch, D and Clough, B and Domart, M-C and Encheva, V and Bando, H and Snijders, AP and Collinson, LM and Yamamoto, M and Shenoy, AR and Frickel, E-M},
doi = {10.1016/j.celrep.2020.108008},
journal = {Cell Reports},
pages = {1--22},
title = {Human GBP1 differentially targets salmonella and toxoplasma to license recognition of microbial ligands and caspase-mediated death},
url = {http://dx.doi.org/10.1016/j.celrep.2020.108008},
volume = {32},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Interferon-inducible guanylate-binding proteins (GBPs) promote cell-intrinsic defense through host cell death. GBPs target pathogens and pathogen-containing vacuoles and promote membrane disruption for release of microbial molecules that activate inflammasomes. GBP1 mediates pyroptosis or atypical apoptosis of Salmonella Typhimurium (STm)- or Toxoplasma gondii (Tg)- infected human macrophages, respectively. The pathogen-proximal detection-mechanisms of GBP1 remain poorly understood, as humans lack functional immunity-related GTPases (IRGs) that assist murine Gbps. Here, we establish that GBP1 promotes the lysis of Tg-containing vacuoles and parasite plasma membranes, releasing Tg-DNA. In contrast, we show GBP1 targets cytosolic STm and recruits caspase-4 to the bacterial surface for its activation by lipopolysaccharide (LPS), but does not contribute to bacterial vacuole escape. Caspase-1 cleaves and inactivates GBP1, and a cleavage-deficient GBP1D192E mutant increases caspase-4-driven pyroptosis due to the absence of feedback inhibition. Our studies elucidate microbe-specific roles of GBP1 in infection detection and its triggering of the assembly of divergent caspase signaling platforms.
AU  - Fisch,D
AU  - Clough,B
AU  - Domart,M-C
AU  - Encheva,V
AU  - Bando,H
AU  - Snijders,AP
AU  - Collinson,LM
AU  - Yamamoto,M
AU  - Shenoy,AR
AU  - Frickel,E-M
DO  - 10.1016/j.celrep.2020.108008
EP  - 22
PY  - 2020///
SN  - 2211-1247
SP  - 1
TI  - Human GBP1 differentially targets salmonella and toxoplasma to license recognition of microbial ligands and caspase-mediated death
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2020.108008
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000560042600010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.sciencedirect.com/science/article/pii/S2211124720309931?via%3Dihub
UR  - http://hdl.handle.net/10044/1/82083
VL  - 32
ER  -
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