dendritic cells in chronic mycobacterial granulomas restrict local anti-bacterial t cell response in a murine model树突细胞在慢性分枝杆菌肉芽肿限制局部抗菌t细胞反应在一个小鼠模型.pdfVIP

Dendritic Cells in Chronic Mycobacterial Granulomas Restrict Local Anti-Bacterial T Cell Response in a Murine Model Heidi A. Schreiber1,2*, Paul D. Hulseberg 1,2, JangEun Lee 1¤a, Jozsef Prechl 1¤b, Peter Barta3, Nora Szlavik4, Jeffrey S. Harding 1,2, Zsuzsanna Fabry 1,2, Matyas Sandor 1,2 1 Department of Pathology and Laboratory Medicine, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin, United States of America, 2 Cellular and Molecular Pathology Training Program, University of Wisconsin, Madison, Wisconsin, United States of America, 3 Department of Pulmonology, Semmelweis University, Budapest, Hungary, 4 Sejtdiagnosztika Kft, Hospital Bajcsy Zsilinszky, Budapest, Hungary Abstract Background: Mycobacterium-induced granulomas are the interface between bacteria and host immune response. During acute infection dendritic cells (DCs) are critical for mycobacterial dissemination and activation of protective T cells. However, their role during chronic infection in the granuloma is poorly understood. Methodology/Principal Findings: We report that an inflammatory subset of murine DCs are present in granulomas induced by Mycobacteria bovis strain Bacillus Calmette-guerin (BCG), and both their location in granulomas and costimulatory molecule expression changes throughout infection. By flow cytometric analysis, we found that CD11c+ cells in chronic granulomas had lower expression of MHCII and co-stimulatory molecules CD40, CD80 and CD86, and higher expression of inhibitory molecules PD-L1 and PD-L2 compared to CD11c+ cells from acute granulomas. As a consequence of their phenotype, CD11c+ cells from chronic lesions were unable to support the reactivation of newly-recruited, antigen 85B- specific CD4+ +