PMID- 26409283
OWN - NLM
STAT- MEDLINE
DCOM- 20160711
LR  - 20211203
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 61Suppl 3
IP  - Suppl 3
DP  - 2015 Oct 15
TI  - Immune Cell Regulatory Pathways Unexplored as Host-Directed Therapeutic Targets 
      for Mycobacterium tuberculosis: An Opportunity to Apply Precision Medicine 
      Innovations to Infectious Diseases.
PG  - S200-16
LID - 10.1093/cid/civ621 [doi]
AB  - The lack of novel antimicrobial drugs in development for tuberculosis treatment 
      has provided an impetus for the discovery of adjunctive host-directed therapies 
      (HDTs). Several promising HDT candidates are being evaluated, but major 
      advancement of tuberculosis HDTs will require understanding of the master or 
      "core" cell signaling pathways that control intersecting immunologic and 
      metabolic regulatory mechanisms, collectively described as "immunometabolism." 
      Core regulatory pathways conserved in all eukaryotic cells include poly 
      (ADP-ribose) polymerases (PARPs), sirtuins, AMP-activated protein kinase (AMPK), 
      and mechanistic target of rapamycin (mTOR) signaling. Critical interactions of 
      these signaling pathways with each other and their roles as master regulators of 
      immunometabolic functions will be addressed, as well as how Mycobacterium 
      tuberculosis is already known to influence various other cell signaling pathways 
      interacting with them. Knowledge of these essential mechanisms of cell function 
      regulation has led to breakthrough targeted treatment advances for many diseases, 
      most prominently in oncology. Leveraging these exciting advances in precision 
      medicine for the development of innovative next-generation HDTs may lead to 
      entirely new paradigms for treatment and prevention of tuberculosis and other 
      infectious diseases.
CI  - Published by Oxford University Press on behalf of the Infectious Diseases Society 
      of America 2015. This work is written by (a) US Government employee(s) and is in 
      the public domain in the US.
FAU - Mahon, Robert N
AU  - Mahon RN
AD  - Division of AIDS-Henry M. Jackson Foundation for the Advancement of Military 
      Medicine, Inc, Contractor to the National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health.
FAU - Hafner, Richard
AU  - Hafner R
AD  - Division of AIDS, National Institute of Allergy and Infectious Diseases, National 
      Institutes of Health, Bethesda, Maryland.
LA  - eng
GR  - HHSN272200800014C/AI/NIAID NIH HHS/United States
GR  - HHSN272200800014C/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Antitubercular Agents)
RN  - EC 2.4.2.30 (PARP1 protein, human)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Antitubercular Agents/*therapeutic use
MH  - Humans
MH  - Mycobacterium tuberculosis/drug effects
MH  - Poly (ADP-Ribose) Polymerase-1
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - *Precision Medicine/methods
MH  - Signal Transduction/drug effects/genetics
MH  - Sirtuins/metabolism
MH  - TOR Serine-Threonine Kinases/immunology/metabolism
MH  - Tuberculosis/*drug therapy/immunology/*metabolism/prevention & control
PMC - PMC4583576
OTO - NOTNLM
OT  - host-directed therapy
OT  - immunometabolism
OT  - precision medicine
OT  - signaling pathways
OT  - tuberculosis
EDAT- 2015/09/27 06:00
MHDA- 2016/07/12 06:00
PMCR- 2016/10/15
CRDT- 2015/09/27 06:00
PHST- 2015/09/27 06:00 [entrez]
PHST- 2015/09/27 06:00 [pubmed]
PHST- 2016/07/12 06:00 [medline]
PHST- 2016/10/15 00:00 [pmc-release]
AID - civ621 [pii]
AID - 10.1093/cid/civ621 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2015 Oct 15;61Suppl 3(Suppl 3):S200-16. doi: 10.1093/cid/civ621.