title: Carbon dioxide-sensing in organisms and its implications for human disease.
abstract: The capacity of organisms to sense changes in the levels of internal and external gases and to respond accordingly is central to a range of physiologic and pathophysiologic processes. Carbon dioxide, a primary product of oxidative metabolism is one such gas that can be sensed by both prokaryotic and eukaryotic cells and in response to altered levels, elicit the activation of multiple adaptive pathways. The outcomes of activating CO2-sensitive pathways in various species include increased virulence of fungal and bacterial pathogens, prey-seeking behavior in insects as well as taste perception, lung function, and the control of immunity in mammals. In this review, we discuss what is known about the mechanisms underpinning CO2 sensing across a range of species and consider the implications of this for physiology, disease progression, and the possibility of developing new therapeutics for inflammatory and infectious disease.
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Eoin P
authors.initials: EP
authors.lastname: Cummins
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Selfridge
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sporn
authors.forename: Jacob I
authors.initials: JI
authors.lastname: Sznajder
authors.forename: Cormac T
authors.initials: CT
authors.lastname: Taylor
mesh_terms: D000220:Adaptation, Biological / Q000502:physiology*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000502:physiology*; D017630:Connexins / Q000378:metabolism; D006801:Humans; D007239:Infections / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D050296:Microbial Viability; D008954:Models, Biological; D012119:Respiration; D015398:Signal Transduction / Q000502:physiology*; D013045:Species Specificity
chemical_list: D020346:Aquaporins; D017630:Connexins; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases; D000262:Adenylyl Cyclases
references.citation: Am J Respir Crit Care Med. 2001 Sep 1;164(5):802-6
references.pmid: 11549536
references.citation: J Neurosci. 2011 Sep 7;31(36):12880-8
references.pmid: 21900566
references.citation: J Immunol. 2010 Oct 1;185(7):4439-45
references.pmid: 20817876
references.citation: Crit Care Med. 2008 Jul;36(7):2128-35
references.pmid: 18552698
references.citation: Am J Respir Crit Care Med. 2004 Jan 1;169(1):46-56
references.pmid: 12958048
references.citation: Curr Biol. 2013 Feb 18;23(4):301-6
references.pmid: 23352695
references.citation: Am J Physiol. 1998 Feb;274(2):C543-8
references.pmid: 9486145
references.citation: N Engl J Med. 1998 Feb 5;338(6):347-54
references.pmid: 9449727
references.citation: Chest. 2003 Aug;124(2):459-67
references.pmid: 12907529
references.citation: N Engl J Med. 2000 May 4;342(18):1301-8
references.pmid: 10793162
references.citation: Curr Biol. 2012 Dec 18;22(24):2294-302
references.pmid: 23142045
references.citation: Proc Natl Acad Sci U S A. 2004 May 18;101(20):7497-8
references.pmid: 15138305
references.citation: Mol Cell Biol. 2001 Apr;21(7):2496-505
references.pmid: 11259598
references.citation: Chest. 1982 Sep;82(3):310-4
references.pmid: 7105857
references.citation: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7769-73
references.pmid: 12032358
references.citation: Curr Biol. 2011 Mar 8;21(5):377-83
references.pmid: 21353558
references.citation: Mol Biol Cell. 2012 Jul;23(14):2692-701
references.pmid: 22621896
references.citation: Genes Dev. 2012 Feb 1;26(3):203-34
references.pmid: 22302935
references.citation: Microbes Infect. 2001 Aug;3(10):799-808
references.pmid: 11580974
references.citation: Pharmacol Ther. 1997;74(1):1-20
references.pmid: 9336012
references.citation: Crit Care Med. 2005 Nov;33(11):2606-12
references.pmid: 16276187
references.citation: J Exp Biol. 2005 Aug;208(Pt 15):2963-72
references.pmid: 16043601
references.citation: FASEB J. 2010 Jul;24(7):2178-90
references.pmid: 20181940
references.citation: Science. 2000 Jul 28;289(5479):625-8
references.pmid: 10915626
references.citation: J Physiol. 2010 Oct 15;588(Pt 20):3921-31
references.pmid: 20736419
references.citation: J Biol Chem. 2009 Jan 9;284(2):784-91
references.pmid: 19008230
references.citation: PLoS One. 2012;7(10):e46696
references.pmid: 23056407
references.citation: Microbiology (Reading). 2013 Aug;159(Pt 8):1748-1759
references.pmid: 23728627
references.citation: J Exp Biol. 2009 Aug;212(Pt 15):2303-12
references.pmid: 19617422
references.citation: Science. 2007 Aug 17;317(5840):953-7
references.pmid: 17702944
references.citation: Science. 2009 Oct 16;326(5951):443-5
references.pmid: 19833970
references.citation: J Exp Biol. 2012 Nov 15;215(Pt 22):3865-73
references.pmid: 23100485
references.citation: Adv Exp Med Biol. 2008;605:322-6
references.pmid: 18085293
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Oct;283(4):L665-70
references.pmid: 12225940
references.citation: Mol Cell. 2008 May 23;30(4):393-402
references.pmid: 18498744
references.citation: Curr Biol. 2009 Feb 24;19(4):330-4
references.pmid: 19200725
references.citation: Am J Physiol Lung Cell Mol Physiol. 2009 Apr;296(4):L657-65
references.pmid: 19136578
references.citation: Thorax. 2009 Nov;64(11):976-82
references.pmid: 19617214
references.citation: Microbiology (Reading). 2010 Jan;156(Pt 1):23-29
references.pmid: 19833770
references.citation: Genetics. 2011 Dec;189(4):1327-39
references.pmid: 21954162
references.citation: Am Rev Respir Dis. 1990 Aug;142(2):311-5
references.pmid: 2200314
references.citation: Am J Med. 2005 Feb;118(2):145-50
references.pmid: 15694899
references.citation: Cold Spring Harb Perspect Biol. 2012 Dec 01;4(12):
references.pmid: 23209152
references.citation: Mol Biol Evol. 2002 Dec;19(12):2239-46
references.pmid: 12446814
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):4024-9
references.pmid: 19237558
references.citation: Am J Respir Crit Care Med. 2006 Mar 15;173(6):659-66
references.pmid: 16387803
references.citation: Chin Med J (Engl). 2010 Aug;123(16):2254-8
references.pmid: 20819675
references.citation: Microsc Res Tech. 1999 Dec 15;47(6):416-27
references.pmid: 10607381
references.citation: J Immunol. 2004 Aug 1;173(3):1934-40
references.pmid: 15265927
references.citation: Physiology (Bethesda). 2010 Oct;25(5):272-9
references.pmid: 20940432
references.citation: J Bacteriol. 2007 Jan;189(2):437-45
references.pmid: 17098904
references.citation: Respir Physiol. 2001 Dec;129(1-2):101-21
references.pmid: 11738649
references.citation: J Biol Chem. 2000 Jan 28;275(4):2686-92
references.pmid: 10644730
references.citation: Nature. 2013 May 2;497(7447):13-4
references.pmid: 23636369
references.citation: J Physiol. 2013 Jun 1;591(11):2763-5
references.pmid: 23729790
references.citation: Am J Respir Crit Care Med. 2002 Aug 1;166(3):403-8
references.pmid: 12153979
references.citation: Eur Respir J. 2008 Nov;32(5):1386-98
references.pmid: 18978138
references.citation: Proc Natl Acad Sci U S A. 1973 Sep;70(9):2505-8
references.pmid: 4200327
references.citation: Respir Physiol Neurobiol. 2012 Dec 1;184(3):309-15
references.pmid: 22705499
references.citation: Respir Physiol Neurobiol. 2010 Oct 31;173(3):193-4
references.pmid: 20553979
references.citation: J Mol Biol. 2006 Sep 29;362(4):623-39
references.pmid: 16934836
references.citation: Chemphyschem. 2011 Apr 4;12(5):1017-9
references.pmid: 21384488
references.citation: Lancet. 1978 Feb 18;1(8060):360-2
references.pmid: 75398
references.citation: J Physiol. 1905 May 9;32(3-4):225-66
references.pmid: 16992774
references.citation: Am J Respir Cell Mol Biol. 2008 Jan;38(1):32-7
references.pmid: 17690328
references.citation: Am J Respir Cell Mol Biol. 2003 Jul;29(1):124-32
references.pmid: 12600832
references.citation: Sensors (Basel). 2011;11(2):2112-28
references.pmid: 21544217
references.citation: Curr Opin Struct Biol. 2006 Dec;16(6):736-43
references.pmid: 17015012
references.citation: Am Rev Respir Dis. 1988 May;137(5):1159-64
references.pmid: 3057957
references.citation: Cell. 2012 Feb 3;148(3):399-408
references.pmid: 22304911
references.citation: J Enzyme Inhib Med Chem. 2013 Apr;28(2):267-77
references.pmid: 23137351
references.citation: Nature. 2011 Jun 2;474(7349):87-91
references.pmid: 21637258
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Jul;289(1):L96-L103
references.pmid: 15778246
references.citation: Chest. 2012 Nov;142(5):1193-1199
references.pmid: 22677348
references.citation: Am J Respir Cell Mol Biol. 2013 Nov;49(5):821-8
references.pmid: 23777386
references.citation: Anesthesiology. 2008 Nov;109(5):837-48
references.pmid: 18946296
references.citation: Nat Cell Biol. 2010 Jan;12(1):87-93; sup pp 1-18
references.pmid: 20010812
references.citation: Curr Biol. 2005 Nov 22;15(22):2013-20
references.pmid: 16303560
references.citation: J Biol Chem. 2012 Apr 20;287(17):14004-11
references.pmid: 22396550
references.citation: J Biol Chem. 2011 Oct 28;286(43):37067-76
references.pmid: 21903582
references.citation: Curr Biol. 2005 Nov 22;15(22):2021-6
references.pmid: 16303561
references.citation: Nature. 2004 Oct 14;431(7010):854-9
references.pmid: 15372051
references.citation: Am J Respir Cell Mol Biol. 2013 May;48(5):626-34
references.pmid: 23349050
references.citation: J Physiol. 2013 Jun 1;591(11):2773
references.pmid: 23729793
references.citation: Eukaryot Cell. 2006 Jan;5(1):103-11
references.pmid: 16400172
references.citation: JAMA. 1973 Aug 13;225(7):705-7
references.pmid: 4740475
references.citation: J Clin Invest. 2008 Feb;118(2):752-62
references.pmid: 18188452
references.citation: J Physiol. 2010 Mar 1;588(Pt 5):861-72
references.pmid: 20051495
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):8038-43
references.pmid: 18524955
references.citation: Curr Opin Microbiol. 2006 Dec;9(6):572-8
references.pmid: 17045514
references.citation: EMBO J. 2011 Apr 20;30(8):1645-58
references.pmid: 21423149
references.citation: J Physiol. 2011 Feb 15;589(Pt 4):797-803
references.pmid: 21224229
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2041-6
references.pmid: 19181845
references.citation: Crit Care Med. 2009 Nov;37(11):2953-61
references.pmid: 19773647
references.citation: J Physiol. 2011 Dec 1;589(Pt 23):5561-79
references.pmid: 22005672
references.citation: Transfus Clin Biol. 2006 Mar-Apr;13(1-2):103-10
references.pmid: 16563833
references.citation: Nature. 2007 Jan 4;445(7123):86-90
references.pmid: 17167414
references.citation: Nature. 2003 Oct 16;425(6959):734-7
references.pmid: 14520414
references.citation: EMBO J. 2012 May 30;31(11):2448-60
references.pmid: 22562152
references.citation: PLoS One. 2008 Jul 30;3(7):e2793
references.pmid: 18665214
references.citation: J Clin Invest. 1985 Aug;76(2):508-16
references.pmid: 3928681
references.citation: J Gen Intern Med. 2003 Oct;18(10):824-30
references.pmid: 14521645
references.citation: J Exp Bot. 2008;59(7):1615-24
references.pmid: 17975207
references.citation: J Bacteriol. 2008 Oct;190(19):6483-92
references.pmid: 18676674
references.citation: J Physiol. 2010 Jul 1;588(Pt 13):2455-71
references.pmid: 20421288
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18710-5
references.pmid: 19846771
references.citation: J Biol Chem. 2008 Sep 12;283(37):25340-25347
references.pmid: 18617525
references.citation: Infect Immun. 1985 Aug;49(2):455-6
references.pmid: 3926652
references.citation: J Insect Sci. 2009;9:19
references.pmid: 19613462
references.citation: Proc Natl Acad Sci U S A. 2006 May 9;103(19):7506-11
references.pmid: 16651523
references.citation: PLoS One. 2007 Nov 28;2(11):e1238
references.pmid: 18043745
references.citation: Ann Surg. 1997 Aug;226(2):179-90
references.pmid: 9296512
references.citation: Crit Care Med. 2008 Dec;36(12):3135-44
references.pmid: 18936707
references.citation: Neuron. 2011 Mar 24;69(6):1099-113
references.pmid: 21435556
references.citation: J Physiol. 2013 Jun 1;591(11):2767-9
references.pmid: 23729791
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5406-11
references.pmid: 19273840
references.citation: J Exp Zool A Ecol Genet Physiol. 2010 Nov 1;313(9):618-21
references.pmid: 20683854
references.citation: FEBS Lett. 2010 Sep 24;584(18):3985-9
references.pmid: 20691686
references.citation: Lancet. 1999 Oct 9;354(9186):1283-6
references.pmid: 10520649
references.citation: J Physiol. 2013 Jun 1;591(11):2771-2
references.pmid: 23729792
references.citation: PLoS One. 2009;4(3):e4904
references.pmid: 19295911
references.citation: PLoS Pathog. 2010 Nov 18;6(11):e1001193
references.pmid: 21124988
references.citation: Infect Immun. 2009 Sep;77(9):4111-20
references.pmid: 19564378
references.citation: Infect Immun. 2003 Nov;71(11):6155-64
references.pmid: 14573631
references.citation: Mycopathologia. 2009 Jun;167(6):307-14
references.pmid: 19130292
references.citation: J Biol Chem. 2012 Jul 27;287(31):26291-301
references.pmid: 22654111
references.citation: Adv Exp Med Biol. 2010;679:1-17
references.pmid: 20666220
references.citation: Science. 2010 Jan 15;327(5963):275-6
references.pmid: 20075235
references.citation: Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):254-9
references.pmid: 21173231
references.citation: Annu Rev Plant Biol. 2010;61:561-91
references.pmid: 20192751
references.citation: PLoS One. 2012;7(10):e47635
references.pmid: 23112828
references.citation: Cell Commun Signal. 2010 Jun 25;8:15
references.pmid: 20579354
references.citation: Biophys J. 1997 Aug;73(2):798-806
references.pmid: 9251796