Role of Metabolic Reprogramming in Pulmonary Innate Immunity and Its Impact on Lung Diseases

Journal of Innate Immunity - Tập 12 Số 1 - Trang 31-46 - 2020
Charalambos Michaeloudes1, Pankaj Bhavsar1, Sharon Mumby1, Bingling Xu2, Christopher Hui2, Gaetano Caramori1, Ian M. Adcock1
1Experimental Studies and Cell and Molecular Biology, Airway Disease Section, National Heart and Lung Institute, Imperial College London and Biomedical Research Unit, Royal Brompton Hospital, London, UK
2Respiratory and Critical Care Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China

Tóm tắt

Lung innate immunity is the first line of defence against inhaled allergens, pathogens and environmental pollutants. Cellular metabolism plays a key role in innate immunity. Catabolic pathways, including glycolysis and fatty acid oxidation (FAO), are interconnected with biosynthetic and redox pathways. Innate immune cell activation and differentiation trigger extensive metabolic changes that are required to support their function. Pro-inflammatory polarisation of macrophages and activation of dendritic cells, mast cells and neutrophils are associated with increased glycolysis and a shift towards the pentose phosphate pathway and fatty acid synthesis. These changes provide the macromolecules required for proliferation and inflammatory mediator production and reactive oxygen species for anti-microbial effects. Conversely, anti-inflammatory macrophages use primarily FAO and oxidative phosphorylation to ensure efficient energy production and redox balance required for prolonged survival. Deregulation of metabolic reprogramming in lung diseases, such as asthma and chronic obstructive pulmonary disease, may contribute to impaired innate immune cell function. Understanding how innate immune cell metabolism is altered in lung disease may lead to identification of new therapeutic targets. This is important as drugs targeting a number of metabolic pathways are already in clinical development for the treatment of other diseases such as cancer.

Từ khóa


Tài liệu tham khảo

10.1038/ni.3123

10.1183/09031936.00141514

10.1016/j.it.2017.03.001

10.1126/science.1160809

10.1093/jn/137.6.1616S

10.1038/nature10602

10.1172/JCI69600

10.1007/s13238-014-0082-8

10.1016/j.cmet.2011.03.009

10.2337/diabetes.48.8.1667

10.1042/BST0390001

10.1016/j.molcel.2013.01.019

10.1016/j.molcel.2010.06.022

10.1016/j.molcel.2008.03.003

10.1073/pnas.0705070104

10.1038/nature06322

10.1002/jcb.26399

10.1016/j.mce.2016.11.010

10.1159/000487057

10.4049/jimmunol.175.3.1609

10.1016/j.jaci.2006.03.041

10.1513/AnnalsATS.201403-097AW

10.1007/s00424-017-1965-3

10.1007/978-3-319-54090-0_12

10.1016/j.imbio.2017.11.001

10.1016/j.immuni.2014.06.008

10.4049/jimmunol.1203420

10.2147/COPD.S152291

10.1586/1744666X.2013.851347

10.1016/S2213-2600(13)70128-0

10.1038/s41577-018-0006-6

10.1136/thorax.57.10.875

10.4049/jimmunol.1302984

10.1111/j.1365-2222.2008.02971.x

10.4049/jimmunol.181.5.3540

10.4049/jimmunol.0900228

10.1038/srep18575

10.1172/JCI82925

10.1371/journal.pone.0183066

10.1111/j.1365-2222.2011.03860.x

10.1016/j.immuni.2015.07.007

10.1038/ni.2833

10.1126/science.1250684

10.1111/j.1365-2222.2010.03520.x

10.1038/s41467-018-04804-6

10.1126/science.aaj2155

10.1038/ni.3421

10.1159/000312122

10.1111/j.1365-201X.1968.tb10852.x

10.1038/bjp.2008.148

10.1016/S0091-6749(98)70122-8

10.2353/ajpath.2010.100019

10.1186/1465-9921-15-72

10.1152/ajplung.00341.2014

10.1182/blood-2009-08-236711

10.1165/rcmb.2015-0295OC

10.1016/j.cmet.2015.01.017

10.1016/j.immuni.2015.02.005

10.1038/nature20117

10.1038/nature11986

10.1016/j.cmet.2006.05.011

10.7554/eLife.11612

10.1016/j.cmet.2012.04.023

10.1006/bbrc.1995.1094

10.1111/cea.12947

10.1038/ni.3366

10.1016/j.cmet.2018.06.001

10.1016/j.bbalip.2014.06.007

10.1152/ajplung.00208.2018

10.1165/rcmb.2017-0061OC

10.1084/jem.160.6.1656

10.1172/JCI110647

10.3389/fimmu.2018.01404

10.1073/pnas.98.4.1717

10.1183/13993003.02135-2016

10.1038/nrdp.2015.76

10.1038/nri2254

10.1016/j.ccm.2013.11.001

10.1513/AnnalsATS.201402-049AW

10.1096/fj.14-268276

10.1080/15548627.2015.1017190

10.1186/1465-9921-14-97

10.1172/JCI74985

10.1183/09031936.00036709

10.1046/j.1440-1711.2003.t01-1-01170.x

10.1164/rccm.201608-1714OC

10.1183/13993003.02244-2018

10.1038/s41598-019-46045-7

10.3390/jcm5100089

10.1186/s12931-015-0221-7

10.1182/blood-2012-03-416156

10.1111/imm.12437

10.1074/jbc.M115.640094

10.1242/dmm.033027

10.1083/jcb.201503066

10.1038/nm.4027

10.3389/fmicb.2013.00293

10.1074/jbc.M410592200

10.4049/jimmunol.176.3.1733

10.1038/nri3665

10.1016/j.celrep.2017.04.039

10.4049/jimmunol.1501557

10.1073/pnas.1800525115

10.1038/ncomms9873

10.1016/j.virol.2013.06.026

10.3389/fmicb.2016.01127

10.1038/nri2975

10.1016/j.bbamcr.2012.03.005

10.1126/scisignal.2001147

10.1165/rcmb.2015-0231TR

10.1038/ncomms13280

10.7554/eLife.13663

10.1172/JCI78253

10.1002/jcp.27261

10.1186/s12931-018-0931-8

10.1038/cddis.2014.460

10.1126/science.aan4665

10.1126/scitranslmed.aao4583

10.1021/acs.jmedchem.8b00241

10.3389/fonc.2018.00556

10.1183/09031936.00057710

10.1164/rccm.200710-1588OC

10.1124/jpet.113.210138

10.1038/nrc3483

10.1016/j.jaci.2015.01.046

10.1002/mds.23148

10.1111/j.1478-3231.2010.02250.x

10.1136/thoraxjnl-2015-208035

10.1186/s40170-016-0154-8

Thông tin
Thông tin xuất bản

Journal of Innate Immunity

Tập 12 Số 1

31-46

Thông tin tác giả