Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Sci Rep. 2017 Mar 6;7:43578. doi: 10.1038/srep43578.
Mycobacterium tuberculosis-infected macrophages and dendritic cells are limited in their ability to present antigen to CD4+ T cells suggesting that other mechanism of antigen presentation are driving the robust T cell response observed during an M. tuberculosis infection. These mechanisms could include antigens present in apoptotic bodies, necrotic debris, exosomes or even release of non-vesicular antigen from infected cells. However, there is limited data to support any of these mechanisms as important in driving T cell activation in vivo. In the present study we use Rab27a-deficient mice which show diminished trafficking of mycobacterial components to exosomes as well as M. tuberculosis strains that express recombinant proteins which traffic or fail to traffic to exosomes. We observed that exosomes released during a mouse M. tuberculosis infection contribute significantly to its T cell response. These finding imply that exosomes function to promote T cell immunity during a bacterial infection and are an important source of extracellular antigen.
结核分枝杆菌感染的巨噬细胞和树突状细胞向 CD4+T 细胞呈递抗原的能力有限，这表明在结核分枝杆菌感染过程中，其他抗原呈递机制驱动了强烈的 T 细胞反应。这些机制可能包括凋亡小体、坏死碎片、外泌体中存在的抗原，甚至是感染细胞中非囊泡抗原的释放。然而，目前的数据有限，无法支持这些机制中的任何一种作为驱动体内 T 细胞激活的重要因素。在本研究中，我们使用 Rab27a 缺陷型小鼠，其显示分枝杆菌成分向 exosomes 的运输减少，以及表达能够或不能运输到 exosomes 的重组蛋白的结核分枝杆菌菌株。我们观察到，在小鼠结核分枝杆菌感染期间释放的 exosomes 对其 T 细胞反应有重要贡献。这些发现表明，exosomes 在细菌感染期间发挥作用，促进 T 细胞免疫，是细胞外抗原的重要来源。
