A TNF-Regulated Recombinatorial Macrophage Immune Receptor Implicated in Granuloma Formation in Tuberculosis

2011 | journal article. A publication with affiliation to the University of Göttingen.

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​A TNF-Regulated Recombinatorial Macrophage Immune Receptor Implicated in Granuloma Formation in Tuberculosis​
Beham, A. W.; Puellmann, K.; Laird, R.; Fuchs, T.; Streich, R.; Breysach, C. & Raddatz, D. et al.​ (2011) 
PLoS Pathogens7(11) art. e1002375​.​ DOI: https://doi.org/10.1371/journal.ppat.1002375 

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Beham, Alexander W.; Puellmann, Kerstin; Laird, Rebecca; Fuchs, Tina; Streich, Roswita; Breysach, Caroline; Raddatz, Dirk; Oniga, Septimia; Peccerella, Teresa; Findeisen, Peter; Kzhyshkowska, Julia; Gratchev, Alexei; Schweyer, Stefan; Saunders, Bernadette; Wessels, Johannes Theodor; Möbius, Wiebke ; Keane, Joseph; Becker, Heinz; Ganser, Arnold; Neumaier, Michael; Kaminski, Wolfgang E.
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) alpha beta based recombinatorial immune receptor in subpopulations of human and mouse monocytes and macrophages. In vitro, we find that the macrophage-TCR alpha beta induces the release of CCL2 and modulates phagocytosis. TNF blockade suppresses macrophage-TCR alpha beta expression. Infection of macrophages from healthy individuals with mycobacteria triggers formation of clusters that express restricted TCR V beta repertoires. In vivo, TCR alpha beta 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-TCR alpha beta 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.
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PLoS Pathogens 



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