التفاصيل البيبلوغرافية
| العنوان: |
A TNF-Regulated Recombinatorial Macrophage Immune Receptor Implicated in Granuloma Formation in Tuberculosis. |
| المؤلفون: |
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 T., Möbius, Wiebke, Keane, Joseph, Becker, Heinz, Ganser, Arnold, Neumaier, Michael |
| المصدر: |
PLoS Pathogens; Nov2011, Vol. 7 Issue 11, Special section p1-16, 16p, 2 Color Photographs, 1 Diagram, 6 Graphs |
| مصطلحات موضوعية: |
MACROPHAGES, MYCOBACTERIA, TUBERCULOSIS research, T cell receptors, GRANULOMA |
| مستخلص: |
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-TCRab 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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