Imperial College London
Alternate

ProfessorJonFriedland

Faculty of Medicine, Department of Infectious Disease

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 8521j.friedland Website

 
 
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Assistant

 

Ms Teyanna Gaeta +44 (0)20 3313 1943

 
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Location

 

8N21ACommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Friedland:2015:10.4049/​jimmunol.1403110,
author = {Friedland, JS and Sathyamoorthy, T and Tezera, L and Walker, N and Brilha, S and Saraiva, L and Mauri, F and Wilkinson, R and Elkington, P},
doi = {10.4049/jimmunol.1403110},
journal = {Journal of Immunology},
pages = {822--891},
title = {Membrane Type 1 Matrix Metalloproteinase Regulates Monocyte Migration and Collagen Destruction in Tuberculosis},
url = {http://hdl.handle.net/10044/1/24170},
volume = {195},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Tuberculosis (TB) remains a global pandemic and drug resistance is rising. Multicellular granulomaformation is the pathological hallmark of Mycobacterium tuberculosis (Mtb) infection. The membranetype1 MMP (MT1-MMP or MMP-14) is a collagenase that is key in leukocyte migration and collagendestruction. In patients with TB, induced sputum MT1-MMP mRNA levels were increased 5.1-foldcompared to matched controls and correlated positively with extent of lung infiltration on chestradiographs (r=0.483; p<0.05). Mtb infection of primary human monocytes increased MT1-MMPsurface expression 31.7-fold and gene expression 24.5-fold. Mtb-infected monocytes degradedcollagen matrix in an MT1-MMP-dependent manner, and MT1-MMP neutralisation decreased collagendegradation by 73%. In human TB granulomas, MT1-MMP immunoreactivity was observed inmacrophages throughout the granuloma. Monocyte-monocyte networks caused a 17.5-fold increase inMT1-MMP surface expression dependent on p38 MAP kinase and GPCR-dependent signalling.Monocytes migrating towards agarose beads impregnated with conditioned media from Mtb-infectedmonocytes expressed MT1-MMP. Neutralization of MT1-MMP activity decreased this Mtb networkdependentmonocyte migration by 44%. Taken together, we demonstrate that MT1-MMP is central totwo key elements of TB pathogenesis, causing collagen degradation and regulating monocyte migration.
AU  - Friedland,JS
AU  - Sathyamoorthy,T
AU  - Tezera,L
AU  - Walker,N
AU  - Brilha,S
AU  - Saraiva,L
AU  - Mauri,F
AU  - Wilkinson,R
AU  - Elkington,P
DO  - 10.4049/jimmunol.1403110
EP  - 891
PY  - 2015///
SN  - 0022-1767
SP  - 822
TI  - Membrane Type 1 Matrix Metalloproteinase Regulates Monocyte Migration and Collagen Destruction in Tuberculosis
T2  - Journal of Immunology
UR  - http://hdl.handle.net/10044/1/24170
VL  - 195
ER  -
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