期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.00920
关键词
Mycobacterium tuberculosis; macrophage; lysophosphatidylcholine; phagosome maturation; inflammation
类别
资金
- Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare of the Republic of Korea [HI15C0450]
- National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2017R1A6A3A11032251, 2012R1A1A2006349, 2015R1D1A1A01058532]
- National Research Foundation of Korea [2017R1A6A3A11032251, 2012R1A1A2006349, 2015R1D1A1A01058532] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Tuberculosis is caused by the infectious agent Mycobacterium tuberculosis (Mtb). Mtb has various survival strategies, including blockade of phagosome maturation and inhibition of antigen presentation. Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein and is involved in various cellular responses, such as activation of second messengers and bactericidal activity in neutrophils. In this study, macrophages were infected with a low infectious dose of Mtb and treated with LPC to investigate the bactericidal activity of LPC against Mtb. In macrophages infected with Mtb strain, H37Ra or H37Rv, LPC suppressed bacterial growth; however, this effect was suppressed in bone marrow-derived macrophages (BMDMs) isolated from G2A (a G protein-coupled receptor involved in some LPC actions) knockout mice. LPC also promoted phagosome maturation via phosphatidylinositol 3 kinase (PI3K)-p38 mitogen-activated protein kinase (MAPK)-mediated reactive oxygen species production and intracellular Ca2+ release during Mtb infection. In addition, LPC induced increased levels of intracellular cyclic adenosine monophosphate (cAMP) and phosphorylated glycogen synthase kinase 3 beta (GSK3 beta) in Mtb-infected macrophages. Protein kinase A (PKA)-induced phosphorylation of GSK3 beta suppressed activation of NF-kappa B in LPC-treated macrophages during Mtb infection, leading to decreased secretion of pro-inflammatory cytokines and increased secretion of anti-inflammatory cytokines. These results suggest that LPC can effectively control Mtb growth by promoting phagosome maturation via cAMP-induced activation of the PKA-PI3K-p38 MAPK pathway. Moreover, LPC can regulate excessive production of pro-inflammatory cytokines associated with bacterial infection of macrophages.
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