Imperial College London
Alternate

DrGeraldLarrouy-Maumus

Faculty of Natural Sciences, Department of Life Sciences

Reader in Molecular Microbiology
 
 
 
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Contact

 

+44 (0)20 7594 7463g.larrouy-maumus

 
 
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Location

 

3.42Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Hamilton:2021:10.1101/2020.01.14.905075,
author = {Hamilton, C and Olona, A and Leishman, S and MacDonald-Ramsahai, K and Cockcroft, S and Larrouy-Maumus, G and Anand, P},
doi = {10.1101/2020.01.14.905075},
publisher = {bioRxiv},
title = {NLRP3 inflammasome priming and activation are regulated by a novel phosphatidylinositol-dependent mechanism},
url = {http://dx.doi.org/10.1101/2020.01.14.905075},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - Imbalance in lipid homeostasis is associated with discrepancies in immune signalling and is tightly linked to metabolic disorders. The diverse ways in which lipids impact immune signalling, however, remain ambiguous. The phospholipid phosphatidylinositol (PI), which is implicated in numerous immune disorders, is chiefly defined by its phosphorylation status. By contrast, the significance of the two fatty acid chains attached to the PI remains unknown. Here, by employing a mass-spectrometry-based assay, we demonstrate a role for PI acyl group chains in regulating both the priming and activation steps of the NLRP3 inflammasome in mouse macrophages. In response to NLRP3 stimuli, cells deficient in ABC transporter ABCB1, which effluxes lipid derivatives, revealed defective inflammasome activation. Mechanistically, Abcb1-deficiency shifted the total PI configuration exhibiting a reduced ratio of short-chain to long-chain PI-acyl lipids. Consequently, Abcb1-deficiency resulted in rapid degradation of TIRAP, the TLR adaptor protein which binds PI(4,5)-phosphate. Moreover, this accompanied increased NLRP3 phosphorylation at the Ser293 position and blunted inflammasome activation. Exogenously supplementing WT cells with linoleic acid, but not arachidonic acid, reconfigured PI acyl chains. Accordingly, linoleic acid supplementation increased TIRAP degradation, elevated NLRP3 phosphorylation, and abrogated inflammasome activation. Altogether, our study reveals a novel metabolic-inflammatory circuit which contributes to calibrating immune responses.
AU  - Hamilton,C
AU  - Olona,A
AU  - Leishman,S
AU  - MacDonald-Ramsahai,K
AU  - Cockcroft,S
AU  - Larrouy-Maumus,G
AU  - Anand,P
DO  - 10.1101/2020.01.14.905075
PB  - bioRxiv
PY  - 2021///
TI  - NLRP3 inflammasome priming and activation are regulated by a novel phosphatidylinositol-dependent mechanism
UR  - http://dx.doi.org/10.1101/2020.01.14.905075
UR  - http://hdl.handle.net/10044/1/93617
ER  -
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