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

• DOI: 10.1371/journal.ppat.1002375
• Publication Date: 2011-11-17T22:01:24Z
• Authors: Alexander W. Beham; Kerstin Puellmann; Rebecca Laird; Tina Fuchs; Roswita Streich; Caroline Breysach; Dirk Raddatz; Septimia Oniga; Teresa Peccerella; Peter Findeisen; Julia Kzhyshkowska; Alexei Gratchev; Stefan Schweyer; Bernadette Saunders; Johannes T. Wessels; Wiebke Möbius; Joseph Keane; Heinz Becker; Arnold Ganser; Michael Neumaier; Wolfgang E. Kaminski
• Keywords: Macrophage-activating factor

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