Antibacterial effects of vitamin D.
Interaction between vitamin D and the immune system has been recognized for many years, but its relevance to normal human physiology has only become evident in the past 5 years. Studies of innate immune responses to pathogens such as Mycobacterium tuberculosis have shown that pathogen-recognition receptor-mediated activation of localized vitamin D metabolism and signaling is a key event associated with infection. Vitamin D, acting in an intracrine fashion, is able to induce expression of antibacterial proteins and enhance the environment in which they function. The net effect of these actions is to support increased bacterial killing in a variety of cell types. The efficacy of such a response is highly dependent on vitamin D status; in other words, the availability of circulating 25-hydroxyvitamin D for intracrine conversion to active 1,25-dihydroxyvitamin D by the enzyme 25-hydroxyvitamin D-1α-hydroxylase. The potential importance of this mechanism as a determinant of human disease is underlined by increasing awareness of vitamin D insufficiency across the globe. This Review will explore the molecular and cellular systems associated with antibacterial responses to vitamin D in different tissues and possible consequences of such a response for the prevention and treatment of human immune disorders.
Department of Orthopaedic Surgery, Room 410D, Orthopaedic Hospital Research Center, 615 Charles E. Young Drive South, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. mhewison@mednet.ucla.edu
Martin
M
Hewison
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009928:Organ Specificity / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology
D000900:Anti-Bacterial Agents; D014807:Vitamin D
J Steroid Biochem Mol Biol. 2006 Aug;100(4-5):107-16
16777406
Prog Biophys Mol Biol. 2006 Sep;92(1):49-59
16566961
Gastroenterology. 1998 May;114(5):1061-5
9558297
Cell. 2004 Dec 17;119(6):753-66
15607973
FASEB J. 2005 Jul;19(9):1067-77
15985530
Acta Med Indones. 2006 Jan-Mar;38(1):3-5
16479024
Osteoporos Int. 1997;7(5):439-43
9425501
Anticancer Res. 2006 Jul-Aug;26(4A):2531-42
16886661
Epidemiol Infect. 2007 Oct;135(7):1095-6; author reply 1097-8
17352842
Nat Clin Pract Endocrinol Metab. 2008 Feb;4(2):80-90
18212810
Calcif Tissue Int. 2000 Jun;66(6):476-8
10821887
Cell Microbiol. 2010 Nov;12(11):1648-65
20560977
J Biol Chem. 2001 Sep 21;276(38):35482-93
11461902
Immunology. 2006 Aug;118(4):509-19
16895558
Cell Host Microbe. 2009 Jun 18;5(6):527-49
19527881
Am J Respir Crit Care Med. 2007 Jul 15;176(2):208-13
17463418
J Immunol. 2009 Mar 15;182(6):3696-705
19265148
Immunopharmacol Immunotoxicol. 2002 Aug;24(3):335-47
12375732
Nat Rev Immunol. 2007 Mar;7(3):179-90
17318230
J Biol Chem. 2010 Jan 22;285(4):2227-31
19948723
Infect Immun. 1998 Nov;66(11):5314-21
9784538
Placenta. 2007 Feb-Mar;28(2-3):161-9
16513165
Pediatrics. 2006 Nov;118(5):1950-61
17079566
Nature. 2001 May 31;411(6837):603-6
11385577
J Clin Endocrinol Metab. 2010 Jul;95(7):3111-7
20427501
Science. 2000 Dec 1;290(5497):1717-21
11099404
Am J Pathol. 2002 Jul;161(1):105-14
12107095
J Leukoc Biol. 2000 Dec;68(6):785-92
11129645
Pediatr Infect Dis J. 2008 Oct;27(10):941-2
18776821
Nutr Rev. 2009 May;67(5):289-93
19386033
J Biol Chem. 2008 Sep 12;283(37):25596-25605
18628207
JPEN J Parenter Enteral Nutr. 2007 Jul-Aug;31(4):311-9
17595441
Endocrinology. 2008 Oct;149(10):4799-808
18535110
J Invest Dermatol. 2007 Mar;127(3):510-2
17299432
J Clin Endocrinol Metab. 2010 Jul;95(7):3368-76
20427486
Semin Reprod Med. 2007 Jan;25(1):21-39
17205421
Immunology. 1986 Jan;57(1):159-63
3002968
J Soc Gynecol Investig. 2004 Jul;11(5):263-71
15219879
J Immunol. 2008 Nov 15;181(10):7115-20
18981132
Inflamm Bowel Dis. 2006 Dec;12(12):1162-74
17119391
PLoS One. 2009 Jun 05;4(6):e5810
19503839
Annu Rev Immunol. 2002;20:197-216
11861602
Trends Endocrinol Metab. 1997 Aug;8(6):245-51
18406812
J Cyst Fibros. 2007 Nov 30;6(6):403-10
17467345
Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G208-16
17962355
Eur Respir J. 2010 May;35(5):1106-12
19797128
J Transl Med. 2009 Apr 23;7:28
19389235
Nature. 2001 May 31;411(6837):599-603
11385576
Ann Epidemiol. 2009 Feb;19(2):73-8
18329892
J Immunol. 2009 Apr 1;182(7):4289-95
19299728
BMC Genomics. 2009 Jul 16;10:321
19607716
Biol Reprod. 2006 Dec;75(6):816-22
16957024
N Engl J Med. 2007 Jul 19;357(3):266-81
17634462
J Immunol. 2009 Nov 1;183(9):5788-98
19812202
Clin Infect Dis. 2009 Feb 15;48(4):418-24
19133797
J Clin Invest. 1983 Nov;72(5):1856-60
6688814
J Clin Invest. 2007 Mar;117(3):803-11
17290304
J Clin Endocrinol Metab. 2001 Feb;86(2):888-94
11158062
J Immunol. 2004 Sep 1;173(5):2909-12
15322146
J Clin Endocrinol Metab. 2010 Feb;95(2):471-8
20133466
Epidemiol Infect. 2006 Dec;134(6):1129-40
16959053
Curr HIV Res. 2007 Jul;5(4):410-5
17627504
Anticancer Res. 2009 Mar;29(3):817-21
19414314
BMC Immunol. 2007 Mar 30;8:5
17397543
J Exp Med. 1992 Apr 1;175(4):1111-22
1552282
Autoimmun Rev. 2010 Sep;9(11):709-15
20601202
Biol Reprod. 2009 Mar;80(3):398-406
19005165
Endocr Relat Cancer. 2010 Jan 29;17(1):R19-38
19926709
J Clin Invest. 1979 Jul;64(1):218-25
312811
Prog Biophys Mol Biol. 2006 Sep;92(1):60-4
16563470
Nat Rev Immunol. 2006 Jan;6(1):9-20
16493424
J Biol Chem. 2008 May 30;283(22):15309-18
18362142
Cell Death Differ. 2005 Oct;12(10):1297-309
15905882
World J Gastroenterol. 2008 Sep 28;14(36):5499-503
18810765
Curr Opin Infect Dis. 2009 Jun;22(3):292-301
19352175
N Engl J Med. 1981 Aug 20;305(8):440-3
6894783
J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):228-33
20152900
N Engl J Med. 2002 Oct 10;347(15):1151-60
12374875
Am J Pathol. 2004 Sep;165(3):807-13
15331405
J Bone Miner Res. 2003 Mar;18(3):579-82
12619944
Science. 2006 Mar 24;311(5768):1770-3
16497887
Lancet. 1979 Mar 24;1(8117):627-30
85869
J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):552-7
17368184
J Exp Med. 1985 Apr 1;161(4):755-65
3838552
Nat Rev Immunol. 2009 May;9(5):313-23
19343057
Gut. 2004 Aug;53(8):1129-36
15247180
Immunol Rev. 2009 Jan;227(1):203-20
19120486
Cell Host Microbe. 2009 Sep 17;6(3):231-43
19748465
J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):793-8
17223549
Hum Genet. 1986 Apr;72(4):281-93
3516862
Lancet. 2010 Jul 17;376(9736):180-8
20541252
Mol Endocrinol. 2003 Dec;17(12):2386-92
14500760
J Bone Miner Res. 2006 Sep;21(9):1496-9
16939409
Nat Rev Immunol. 2003 Sep;3(9):710-20
12949495
J Am Coll Nutr. 2003 Apr;22(2):142-6
12672710
J Invest Dermatol. 2008 Jan;128(1):223-36
17805349
Am J Clin Nutr. 2007 Nov;86(5):1376-83
17991649
J Immunol Methods. 1997 Aug 7;206(1-2):53-9
9328568
J Infect. 2005 Jun;50(5):432-7
15907552
Nat Immunol. 2003 Mar;4(3):269-73
12548285
Am J Respir Crit Care Med. 2009 May 1;179(9):843-50
19179490
J Immunol. 2008 Nov 15;181(10):7090-9
18981129
Thorax. 2010 Mar;65(3):215-20
19996341
Endocrinology. 2010 Jun;151(6):2423-32
20392825