Mycobacterium tuberculosis Membrane Vesicles Inhibit T Cell Activation.

Autor:	Athman JJ; Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106., Sande OJ; Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106.; Department of Molecular Biology and Microbiology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106., Groft SG; Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106., Reba SM; Department of Molecular Biology and Microbiology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106., Nagy N; Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106., Wearsch PA; Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106., Richardson ET; Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106.; Medical Scientist Training Program, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106., Rojas R; Department of Molecular Biology and Microbiology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106.; Center for AIDS Research, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106; and., Boom WH; Department of Molecular Biology and Microbiology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106.; Center for AIDS Research, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106; and.; Division of Infectious Diseases and HIV Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106., Shukla S; Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106., Harding CV; Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106; cvh3@cwru.edu.; Center for AIDS Research, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106; and.; Division of Infectious Diseases and HIV Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2017 Mar 01; Vol. 198 (5), pp. 2028-2037. Date of Electronic Publication: 2017 Jan 25.
DOI:	10.4049/jimmunol.1601199
Abstrakt:	Mycobacterium tuberculosis utilizes multiple mechanisms to evade host immune responses, and inhibition of effector CD4 + T cell responses by M. tuberculosis may contribute to immune evasion. TCR signaling is inhibited by M. tuberculosis cell envelope lipoglycans, such as lipoarabinomannan and lipomannan, but a mechanism for lipoglycans to traffic from M. tuberculosis within infected macrophages to reach T cells is unknown. In these studies, we found that membrane vesicles produced by M. tuberculosis and released from infected macrophages inhibited the activation of CD4 + T cells, as indicated by reduced production of IL-2 and reduced T cell proliferation. Flow cytometry and Western blot demonstrated that lipoglycans from M. tuberculosis -derived bacterial vesicles (BVs) are transferred to T cells, where they inhibit T cell responses. Stimulation of CD4 + T cells in the presence of BVs induced expression of GRAIL, a marker of T cell anergy; upon restimulation, these T cells showed reduced ability to proliferate, confirming a state of T cell anergy. Furthermore, lipoarabinomannan was associated with T cells after their incubation with infected macrophages in vitro and when T cells were isolated from lungs of M. tuberculosis -infected mice, confirming the occurrence of lipoarabinomannan trafficking to T cells in vivo. These studies demonstrate a novel mechanism for the direct regulation of CD4 + T cells by M. tuberculosis lipoglycans conveyed by BVs that are produced by M. tuberculosis and released from infected macrophages. These lipoglycans are transferred to T cells to inhibit T cell responses, providing a mechanism that may promote immune evasion. (Copyright © 2017 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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