title: A TNF-regulated recombinatorial macrophage immune receptor implicated in granuloma formation in tuberculosis.
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.
authors: Department of Surgery, University of Göttingen, Göttingen, Germany. abeham@chirurgie-goettingen.de
authors: Alexander W
authors: AW
authors: Beham
authors: Kerstin
authors: K
authors: Puellmann
authors: Rebecca
authors: R
authors: Laird
authors: Tina
authors: T
authors: Fuchs
authors: Roswita
authors: R
authors: Streich
authors: Caroline
authors: C
authors: Breysach
authors: Dirk
authors: D
authors: Raddatz
authors: Septimia
authors: S
authors: Oniga
authors: Teresa
authors: T
authors: Peccerella
authors: Peter
authors: P
authors: Findeisen
authors: Julia
authors: J
authors: Kzhyshkowska
authors: Alexei
authors: A
authors: Gratchev
authors: Stefan
authors: S
authors: Schweyer
authors: Bernadette
authors: B
authors: Saunders
authors: Johannes T
authors: JT
authors: Wessels
authors: Wiebke
authors: W
authors: Möbius
authors: Joseph
authors: J
authors: Keane
authors: Heinz
authors: H
authors: Becker
authors: Arnold
authors: A
authors: Ganser
authors: Michael
authors: M
authors: Neumaier
authors: Wolfgang E
authors: WE
authors: Kaminski
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D060152:V(D)J Recombination / Q000276:immunology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha