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A TNF-regulated recombinatorial macrophage immune receptor implicated in granuloma formation in tuberculosis
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نویسنده
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beham a.w. ,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 j.t. ,möbius w. ,keane j. ,becker h. ,ganser a. ,neumaier m. ,kaminski w.e.
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منبع
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plos pathogens - 2011 - دوره : 7 - شماره : 11
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چکیده
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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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آدرس
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department of surgery,university of göttingen,göttingen, Germany, department of hematology,hemostasis,oncology and stem cell transplantation,hannover medical school (mhh),hannover, Germany, department of surgery,university of göttingen,göttingen, Germany, institute for clinical chemistry,university of heidelberg medical faculty mannheim,mannheim, Germany, department of surgery,university of göttingen,göttingen, Germany, department of surgery,university of göttingen,göttingen, Germany, department of medicine,university of göttingen,göttingen, Germany, institute for clinical chemistry,university of heidelberg medical faculty mannheim,mannheim, Germany, institute for clinical chemistry,university of heidelberg medical faculty mannheim,mannheim, Germany, institute for clinical chemistry,university of heidelberg medical faculty mannheim,mannheim, Germany, department of dermatology,university of heidelberg medical faculty mannheim,mannheim,germany,institute of general pathology and pathophysiology,russian academy of medical sciences,moscow, Russian Federation, department of dermatology,university of heidelberg medical faculty mannheim,mannheim,germany,institute of general pathology and pathophysiology,russian academy of medical sciences,moscow, Russian Federation, department of pathology,university of göttingen,göttingen, Germany, medicine,central clinical school,centenary institute of cancer medicine and cell biology,sydney, Australia, department of nephrology/rheumatology,university of göttingen,göttingen, Germany, max-planck-institute of experimental medicine,department of neurogenetics,göttingen, Germany, trinity college dublin,institute of molecular medicine,college green,dublin, Ireland, department of surgery,university of göttingen,göttingen, Germany, department of hematology,hemostasis,oncology and stem cell transplantation,hannover medical school (mhh),hannover, Germany, institute for clinical chemistry,university of heidelberg medical faculty mannheim,mannheim, Germany, institute for clinical chemistry,university of heidelberg medical faculty mannheim,mannheim, Germany
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Authors
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