TY - JOUR AB - Mycobacterium tuberculosis infection is characterized by a strong inflammatory response whereby a few infected macrophages within the granuloma induce sustained cellular accumulation. The mechanisms coordinating this response are poorly characterized. We hypothesized that microparticles (MPs), which are submicron, plasma membrane-derived vesicles released by cells under both physiological and pathological conditions, are involved in this process. Aerosol infection of mice with M. tuberculosis increased CD45+ MPs in the blood after 4 wk of infection, and in vitro infection of human and murine macrophages with mycobacteria enhanced MP release. MPs derived from mycobacteria-infected macrophages were proinflammatory, and when injected into uninfected mice they induced significant neutrophil, macrophage, and dendritic cell recruitment to the injection site. When incubated with naive macrophages, these MPs enhanced proinflammatory cytokine and chemokine release, and they aided in the disruption of the integrity of a respiratory epithelial cell monolayer, providing a mechanism for the egress of cells to the site of M. tuberculosis infection in the lung. In addition, MPs colocalized with the endocytic recycling marker Rab11a within macrophages, and this association increased when the MPs were isolated from mycobacteria-infected cells. M. tuberculosis-derived MPs also carried mycobacterial Ag and were able to activate M. tuberculosis-specific CD4+ T cells in vivo and in vitro in a dendritic cell-dependent manner. Collectively, these data identify an unrecognized role for MPs in host response against M. tuberculosis by promoting inflammation, intercellular communication, and cell migration. Copyright © 2013 by The American Association of Immunologists, Inc. AU - Walters, SB AU - Kieckbusch, J AU - Nagalingam, G AU - Swain, A AU - Latham, SL AU - Grau, GER AU - Britton, WJ AU - Combes, V AU - Saunders, BM DA - 2013/01/15 DO - 10.4049/jimmunol.1201856 EP - 677 JO - Journal of Immunology PY - 2013/01/15 SP - 669 TI - Microparticles from mycobacteria-infected macrophages promote inflammation and cellular migration VL - 190 Y1 - 2013/01/15 Y2 - 2024/03/29 ER -