Imperial College London
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DrCandiceRoufosse

Faculty of Medicine, Department of Immunology and Inflammation

Clinical Reader in Renal Pathology
 
 
 
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Contact

 

+44 (0)20 3313 3280c.roufosse

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Whittington:2023:10.1371/journal.ppat.1011495,
author = {Whittington, AM and Turner, FS and Baark, F and Templeman, S and Kirwan, DE and Roufosse, C and Krishnan, N and Robertson, BD and Chong, DLW and Porter, JC and Gilman, RH and Friedland, JS},
doi = {10.1371/journal.ppat.1011495},
journal = {PLoS Pathogens},
pages = {1--25},
title = {An acidic microenvironment in Tuberculosis increases extracellular matrix degradation by regulating macrophage inflammatory responses},
url = {http://dx.doi.org/10.1371/journal.ppat.1011495},
volume = {19},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Mycobacterium tuberculosis (M.tb) infection causes marked tissue inflammation leading to lung destruction and morbidity. The inflammatory extracellular microenvironment is acidic, however the effect of this acidosis on the immune response to M.tb is unknown. Using RNA-seq we show that acidosis produces system level transcriptional change in M.tb infected human macrophages regulating almost 4000 genes. Acidosis specifically upregulated extracellular matrix (ECM) degradation pathways with increased expression of Matrix metalloproteinases (MMPs) which mediate lung destruction in Tuberculosis. Macrophage MMP-1 and -3 secretion was increased by acidosis in a cellular model. Acidosis markedly suppresses several cytokines central to control of M.tb infection including TNF-α and IFN-γ. Murine studies demonstrated expression of known acidosis signaling G-protein coupled receptors OGR-1 and TDAG-8 in Tuberculosis which are shown to mediate the immune effects of decreased pH. Receptors were then demonstrated to be expressed in patients with TB lymphadenitis. Collectively, our findings show that an acidic microenvironment modulates immune function to reduce protective inflammatory responses and increase extracellular matrix degradation in Tuberculosis. Acidosis receptors are therefore potential targets for host directed therapy in patients.
AU  - Whittington,AM
AU  - Turner,FS
AU  - Baark,F
AU  - Templeman,S
AU  - Kirwan,DE
AU  - Roufosse,C
AU  - Krishnan,N
AU  - Robertson,BD
AU  - Chong,DLW
AU  - Porter,JC
AU  - Gilman,RH
AU  - Friedland,JS
DO  - 10.1371/journal.ppat.1011495
EP  - 25
PY  - 2023///
SN  - 1553-7366
SP  - 1
TI  - An acidic microenvironment in Tuberculosis increases extracellular matrix degradation by regulating macrophage inflammatory responses
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1011495
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37418488
UR  - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011495
UR  - http://hdl.handle.net/10044/1/105315
VL  - 19
ER  -
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