Abstract:
:Cells in homeostasis metabolize glucose mainly through the tricarboxylic acid cycle and oxidative phosphorylation, while activated cells switch their basal metabolism to aerobic glycolysis. In this study, we examined whether metabolic reprogramming toward aerobic glycolysis is important for the host response to Mycobacterium tuberculosis (Mtb). Through transcriptional and metabolite analysis we show that Mtb induces a switch in host cellular metabolism toward aerobic glycolysis in human peripheral blood mononuclear cells (PBMCs). The metabolic switch is TLR2 dependent but NOD2 independent, and is mediated in part through activation of the AKT-mTOR (mammalian target of rapamycin) pathway. We show that pharmacological inhibition of the AKT/mTOR pathway inhibits cellular responses to Mtb both in vitro in human PBMCs, and in vivo in a model of murine tuberculosis. Our findings reveal a novel regulatory layer of host responses to Mtb that will aid understanding of host susceptibility to Mtb, and which may be exploited for host-directed therapy.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Lachmandas E,Beigier-Bompadre M,Cheng SC,Kumar V,van Laarhoven A,Wang X,Ammerdorffer A,Boutens L,de Jong D,Kanneganti TD,Gresnigt MS,Ottenhoff TH,Joosten LA,Stienstra R,Wijmenga C,Kaufmann SH,van Crevel R,Netea MGdoi
10.1002/eji.201546259subject
Has Abstractpub_date
2016-11-01 00:00:00pages
2574-2586issue
11eissn
0014-2980issn
1521-4141journal_volume
46pub_type
杂志文章abstract::From several years, the anticancer effects of Vγ9 T lymphocytes make these cells good candidates for cancer immunotherapies. However, the proved efficacy of γδ Τ cell-based cancer immunotherapies in some clinical trials was minimized due to the inherent toxicity of IL-2, which is essential for the combination therapy ...
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