Glycolytic control of MONOcyte memory

http://bit.ly/1CE0Rcj

bitly reference

video: youtube   

http://youtu.be/R45kldE-ink

AMIE ENTRY   way of  ADVANCED MEDICAL INFORMATIC EDUCATION AND  subject query trained immunity

subject: Trained immunity is secondary to Histone modification.The biochemical characterizations of the β-glucan–trained monocytes revealed elevated aerobic glycolysis with increased glucose consumption and lactate production, and higher intracellular ratio of nicotinamide adenine dinucleotide (NAD+) to its reduced form (NADH). The dectin-1–Akt–mTOR–HIF-1α pathway (mTOR, mammalian target of rapamycin; HIF-1α, hypoxia-inducible factor–1α) was responsible for the metabolic shift induced by β-glucan
object_opposite: reduced basal respiration rate, increased glucose consumption and lactate production, and higher intracellular ratio of nicotinamide adenine dinucleotide (NAD+) to its reduced form (NADH). Note that blockage of the pathway blocked the trained memory
misc: 

https://www.youtube.com/watch?v=R45kldE-ink video on MONOCYTE

/bit.ly/1EJFiab

Trained memory. The dectin-1–Akt–mTOR–HIF-1α pathway (mTOR, mammalian target of rapamycin; HIF-1α, hypoxia-inducible factor–1α) was responsible for the metabolic shift induced by β-glucan
author_year:

Shih-Chin Cheng1, 

Jessica Quintin1, 

Robert A. Cramer2, 

Kelly M. Shepardson2, 

Sadia Saeed3, 

Vinod Kumar4,

Evangelos J. Giamarellos-Bourboulis5, 

Joost H. A. Martens3, 

Nagesha Appukudige Rao3, 

Ali Aghajanirefah3,

Ganesh R. Manjeri6, 

Yang Li4, 

Daniela C. Ifrim1, 

Rob J. W. Arts1, 

Brian M. J. W. van der Veer3, 

Peter M. T. Deen7,

Colin Logie3, 

Luke A. O’Neill8, 

Peter Willems6, 

Frank L. van de Veerdonk1, 

Jos W. M. van der Meer1, 

Aylwin Ng9,10,

Leo A. B. Joosten1, 

Cisca Wijmenga4, 

Hendrik G. Stunnenberg4, 

Ramnik J. Xavier9,10, 

Mihai G. Netea1,*/

September 2014

 http://bit.ly/1CE0Rcj

journal_volume_page: Science 26 Vol. 345 no. 6204 

http://bit.ly/1CE0Rcj

Synopsis

In addition to immune signaling pathways, glycolysis genes were strongly upregulated in terms of histone modification profiling, and this was validated by RNA sequencing of cells from β-glucan–treated mice. The biochemical characterizations of the β-glucan–trained monocytes revealed elevated aerobic glycolysis with reduced basal respiration rate, increased glucose consumption and lactate production, and higher intracellular ratio of nicotinamide adenine dinucleotide (NAD⁺) to its reduced form (NADH). The dectin-1–Akt–mTOR–HIF-1α pathway (mTOR, mammalian target of rapamycin; HIF-1α, hypoxia-inducible factor–1α) was responsible for the metabolic shift induced by β-glucan. Trained immunity was completely abrogated in monocytes from dectin-1–deficient patients. Blocking of the mTOR–HIF-1α pathway by chemical inhibitors inhibited trained immunity. Mice receiving metformin, an adenosine monophosphate–activated protein kinase (AMPK) activator that subsequently inhibits mTOR, lost the trained immunity–induced protection against lethal C. albicans infection. The role of the mTOR–HIF-1α pathway for β-glucan–induced innate immune memory was further validated in myeloid-specific HIF-1α knockout (mHIF-1α KO) mice that, unlike wild-type mice, were not protected against Staphylococcus aureus sepsis.