Research Paper Volume 13, Issue 8 pp 11595—11609
Exosomes derived from mycobacterium tuberculosis-infected MSCs induce a pro-inflammatory response of macrophages
- 1 Jinan People’ s Hospital Affiliated to Shandong First Medical University, Laiwu, Shandong Province, China
- 2 Department of Critical Care Medicine, Penglai Hospital of Traditional Chinese Medicine, Penglai, Shandong Province, China
- 3 Penglai Hospital of Traditional Chinese Medicine, Penglai, Shandong Province, China
- 4 Department of Senile Diseases, Dongying City Shengli Hospital, Dongying, Shandong Province, China
Received: November 30, 2020 Accepted: March 4, 2021 Published: April 19, 2021
https://doi.org/10.18632/aging.202854How to Cite
Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Tuberculosis (TB) is a common infectious disease caused by Mycobacterium tuberculosis (M.tb), and macrophages serve as the primary natural host of M.tb. Mesenchymal stem cells (MSCs)-derived exosomes play an essential role in inflammatory responses. This study aimed to determine the role of exosomes derived from M.tb-infected MSCs (Exo-MSCs-M.tb) on macrophages in vitro and in vivo and the underlying mechanisms. Here, we demonstrated that M.tb infection promoted the production of Exo-MSCs-M.tb, but did not influence MSCs proliferation. Exo-MSCs-M.tb were taken up by macrophages and then induced the pro-inflammatory response of macrophages through elevating the production of TNF-α, RANTES, and iNOS. Also, pro-inflammatory response induced by Exo-MSCs-M.tb displayed a time-dependent pattern in macrophages, in which the highest level of inflammatory response was observed at 72 hours post-infection of MSCs. In addition, the effect of Exo-MSCs-M.tb was mediated through TLR2/4 and MyD88 signaling pathways. Furthermore, Exo-MSCs-M.tb could induce the pro-inflammatory response in mice in vivo, and exosomes isolated from Exo-MSCs-M.tb-treated mice could also promote the pro-inflammatory response. Taken together, these results indicate that Exo-MSCs-M.tb induced the pro-inflammatory response of macrophages through TLRs signaling. This study provides new insight into the potential of MSCs-derived exosomes for the treatment of TB.