A TNF-regulated recombinatorial macrophage immune receptor implicated in granuloma formation in tuberculosis

Beham, AW; Puellmann, K; Laird, R; Fuchs, T; Streich, R; Breysach, C; Raddatz, D; Oniga, S; Peccerella, T; Findeisen, P; Kzhyshkowska, J; Gratchev, A; Schweyer, S; Saunders, B; Wessels, JT; Möbius, W; Keane, J; Becker, H; Ganser, A; Neumaier, M; Kaminski, WE

A TNF-regulated recombinatorial macrophage immune receptor implicated in granuloma formation in tuberculosis

Beham, AW Puellmann, K Laird, R Fuchs, T Streich, R Breysach, C Raddatz, D Oniga, S Peccerella, T Findeisen, P Kzhyshkowska, J Gratchev, A Schweyer, S Saunders, B

Wessels, JT Möbius, W Keane, J Becker, H Ganser, A Neumaier, M Kaminski, WE

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Publication Type:: Journal Article
Citation:: PLoS Pathogens, 2011, 7 (11)
Issue Date:: 2011-11-01

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Field	Value	Language
dc.contributor.author	Beham, AW	en_US
dc.contributor.author	Puellmann, K	en_US
dc.contributor.author	Laird, R	en_US
dc.contributor.author	Fuchs, T	en_US
dc.contributor.author	Streich, R	en_US
dc.contributor.author	Breysach, C	en_US
dc.contributor.author	Raddatz, D	en_US
dc.contributor.author	Oniga, S	en_US
dc.contributor.author	Peccerella, T	en_US
dc.contributor.author	Findeisen, P	en_US
dc.contributor.author	Kzhyshkowska, J	en_US
dc.contributor.author	Gratchev, A	en_US
dc.contributor.author	Schweyer, S	en_US
dc.contributor.author	Saunders, B https://orcid.org/0000-0003-0540-4445	en_US
dc.contributor.author	Wessels, JT	en_US
dc.contributor.author	Möbius, W	en_US
dc.contributor.author	Keane, J	en_US
dc.contributor.author	Becker, H	en_US
dc.contributor.author	Ganser, A	en_US
dc.contributor.author	Neumaier, M	en_US
dc.contributor.author	Kaminski, WE	en_US
dc.date.available	2011-09-28	en_US
dc.date.issued	2011-11-01	en_US
dc.identifier.citation	PLoS Pathogens, 2011, 7 (11)	en_US
dc.identifier.issn	1553-7366	en_US
dc.identifier.uri	http://hdl.handle.net/10453/111322
dc.description.abstract	Macrophages play a central role in host defense against mycobacterial infection and anti- TNF therapy is associated with granuloma disorganization and reactivation of tuberculosis in humans. Here, we provide evidence for the presence of a T cell receptor (TCR) αβ based recombinatorial immune receptor in subpopulations of human and mouse monocytes and macrophages. In vitro, we find that the macrophage-TCRαβ induces the release of CCL2 and modulates phagocytosis. TNF blockade suppresses macrophage-TCRαβ expression. Infection of macrophages from healthy individuals with mycobacteria triggers formation of clusters that express restricted TCR Vβ repertoires. In vivo, TCRαβ bearing macrophages abundantly accumulate at the inner host-pathogen contact zone of caseous granulomas from patients with lung tuberculosis. In chimeric mouse models, deletion of the variable macrophage-TCRαβ or TNF is associated with structurally compromised granulomas of pulmonary tuberculosis even in the presence of intact T cells. These results uncover a TNF-regulated recombinatorial immune receptor in monocytes/macrophages and demonstrate its implication in granuloma formation in tuberculosis. © 2011 Beham et al.	en_US
dc.relation.ispartof	PLoS Pathogens	en_US
dc.relation.isbasedon	10.1371/journal.ppat.1002375	en_US
dc.subject.classification	Virology	en_US
dc.subject.mesh	Monocytes	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Tuberculosis, Pulmonary	en_US
dc.subject.mesh	Granuloma	en_US
dc.subject.mesh	Tumor Necrosis Factor-alpha	en_US
dc.subject.mesh	Receptors, Antigen, T-Cell, alpha-beta	en_US
dc.subject.mesh	Receptors, Tumor Necrosis Factor	en_US
dc.subject.mesh	Chemokine CCL2	en_US
dc.subject.mesh	V(D)J Recombination	en_US
dc.title	A TNF-regulated recombinatorial macrophage immune receptor implicated in granuloma formation in tuberculosis	en_US
dc.type	Journal Article
utslib.citation.volume	11	en_US
utslib.citation.volume	7	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1107 Immunology	en_US
utslib.for	1108 Medical Microbiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	11	en_US
pubs.publication-status	Published	en_US
pubs.volume	7	en_US

Abstract:

Macrophages play a central role in host defense against mycobacterial infection and anti- TNF therapy is associated with granuloma disorganization and reactivation of tuberculosis in humans. Here, we provide evidence for the presence of a T cell receptor (TCR) αβ based recombinatorial immune receptor in subpopulations of human and mouse monocytes and macrophages. In vitro, we find that the macrophage-TCRαβ induces the release of CCL2 and modulates phagocytosis. TNF blockade suppresses macrophage-TCRαβ expression. Infection of macrophages from healthy individuals with mycobacteria triggers formation of clusters that express restricted TCR Vβ repertoires. In vivo, TCRαβ bearing macrophages abundantly accumulate at the inner host-pathogen contact zone of caseous granulomas from patients with lung tuberculosis. In chimeric mouse models, deletion of the variable macrophage-TCRαβ or TNF is associated with structurally compromised granulomas of pulmonary tuberculosis even in the presence of intact T cells. These results uncover a TNF-regulated recombinatorial immune receptor in monocytes/macrophages and demonstrate its implication in granuloma formation in tuberculosis. © 2011 Beham et al.

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http://hdl.handle.net/10453/111322