Mycobacterium tuberculosis Membrane Vesicles Inhibit T Cell Activation.

Jaffre J Athman, Obondo J Sande, Sarah G Groft, Scott M Reba, Nancy Nagy, Pamela A Wearsch, Edward T Richardson, Roxana Rojas, W Henry Boom, Supriya Shukla, Clifford V Harding

Journal of immunology (Baltimore, Md. : 1950) 2017 Mar 01

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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.

Citation

Jaffre J Athman, Obondo J Sande, Sarah G Groft, Scott M Reba, Nancy Nagy, Pamela A Wearsch, Edward T Richardson, Roxana Rojas, W Henry Boom, Supriya Shukla, Clifford V Harding. Mycobacterium tuberculosis Membrane Vesicles Inhibit T Cell Activation. Journal of immunology (Baltimore, Md. : 1950). 2017 Mar 01;198(5):2028-2037