The roles of sphingosine-1-phosphate and its receptor in Mycobacterium tuberculosis infection and novel antibiotics discovery
10.16438/j.0513-4870.2019-0090
- VernacularTitle:鞘氨醇-1-磷酸及其受体在结核分枝杆菌感染和抗生素研发中的作用
- Author:
Jun-feng ZHEN
1
;
Shuang-quan YAN
1
;
Yu-zhu LI
1
;
Jian-ping XIE
1
Author Information
1. Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, School of Life Sciences, Southwest University, Chongqing 400715, China
- Publication Type:Research Article
- Keywords:
italic>Mycobacterium tuberculosis;
sphingosine-1-phosphate;
antigen processing;
regulatory mechanism;
tuberculosis;
rug resistance
- From:
Acta Pharmaceutica Sinica
2019;54(8):1348-1355
- CountryChina
- Language:Chinese
-
Abstract:
Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) infection remains a major public health problem of global concern, largely due to antibiotics resistance, persistence and immune evasion. Sphingolipid bioactive molecules are involved in several important pathophysiological processes. Sphingosine-1-phosphate is a key product of sphingolipid metabolism, and can play a role in two manners: autocrine and/or paracrine. Sphingosine-1-phosphate regulates T cells and a variety of antigen-presenting cells during M. tuberculosis infection, promotes antigen processing and expression in monocytes, is involved in the maturation of phagolysosome, regulates Ca2+ homeostasis, participates in the autophagy of macrophages, inhibits the survival and proliferation of M. tuberculosis within host cells, and effectively reduces the necrosis of the mouse lungs infected by M. tuberculosis. Injection of 20 nmol per mouse sphingosine-1-phosphate inhibited up to 47% of mycobacterial growth in the lung and spleen of mice infected by M. tuberculosis. In this paper, sphingosine-1-phosphate, its receptors and regulatory network were reviewed, and the specific mechanism of sphingosine-1-phosphate inhibiting the survival of M. tuberculosis-infected host cells was elaborated. This will provide novel insights into the new targets for tuberculosis prevention and treatment.
