Osteopontin impairs host defense during established gram-negative sepsis caused by Burkholderia pseudomallei (melioidosis).
BACKGROUND
Melioidosis, caused by infection with Burkholderia (B.) pseudomallei, is a severe illness that is endemic in Southeast Asia. Osteopontin (OPN) is a phosphorylated glycoprotein that is involved in several immune responses including induction of T-helper 1 cytokines and recruitment of inflammatory cells.


RESULTS
OPN levels were determined in plasma from 33 melioidosis patients and 31 healthy controls, and in wild-type (WT) mice intranasally infected with B. pseudomallei. OPN function was studied in experimental murine melioidosis using WT and OPN knockout (KO) mice. Plasma OPN levels were elevated in patients with severe melioidosis, even more so in patients who went on to die. In patients who recovered plasma OPN concentrations had decreased after treatment. In experimental melioidosis in mice plasma and pulmonary OPN levels were also increased. Whereas WT and OPN KO mice were indistinguishable during the first 24 hours after infection, after 72 hours OPN KO mice demonstrated reduced bacterial numbers in their lungs, diminished pulmonary tissue injury, especially due to less necrosis, and decreased neutrophil infiltration. Moreover, OPN KO mice displayed a delayed mortality as compared to WT mice. OPN deficiency did not influence the induction of proinflammatory cytokines.


CONCLUSIONS
These data suggest that sustained production of OPN impairs host defense during established septic melioidosis.
van der Windt
Gerritje J W
GJ
Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands.
Wiersinga
W Joost
WJ
Wieland
Catharina W
CW
Tjia
Ivo C S I
IC
Day
Nicholas P
NP
Peacock
Sharon J
SJ
Florquin
Sandrine
S
van der Poll
Tom
T
D000818:Animals; D016957:Burkholderia pseudomallei / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity*; D015169:Colony Count, Microbial; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008554:Melioidosis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis / Q000473:pathology; D009504:Neutrophils / Q000276:immunology; D053495:Osteopontin / Q000032:analysis / Q000097:blood* / Q000172:deficiency / Q000276:immunology*
D053495:Osteopontin
Chem Res Toxicol. 2006 Feb;19(2):223-33
16485898
Science. 2000 Feb 4;287(5454):860-4
10657301
Int J Exp Pathol. 2000 Dec;81(6):373-90
11298186
Cytokine Growth Factor Rev. 2008 Oct-Dec;19(5-6):333-45
18952487
Lancet. 2003 May 17;361(9370):1715-22
12767750
Infect Immun. 1999 Jul;67(7):3593-600
10377144
Immunology. 2007 Dec;122(4):466-75
17680800
J Immunol. 2005 Nov 1;175(9):6006-13
16237095
J Pathol. 2006 Mar;208(4):473-85
16440289
Int Immunol. 2004 Mar;16(3):477-88
14978021
Cell Microbiol. 2008 Jan;10(1):81-7
17645551
Acta Trop. 2006 Jul;98(3):305-10
16765311
PLoS Med. 2007 Jul 31;4(7):e248
17676990
Crit Care Med. 2003 Apr;31(4):1250-6
12682500
Am J Physiol Gastrointest Liver Physiol. 2004 Jul;287(1):G264-73
15044174
Biochem Biophys Res Commun. 1999 Mar 24;256(3):527-31
10080931
Infect Immun. 2009 Jan;77(1):456-63
18955471
J Leukoc Biol. 2005 May;77(5):710-8
15695554
Science. 2001 Nov 23;294(5547):1731-5
11721059
Crit Care Med. 2003 Apr;31(4 Suppl):S195-9
12682440
Exp Cell Res. 2007 Apr 1;313(6):1149-60
17306792
Infect Immun. 2007 Aug;75(8):3739-46
17517876
J Infect Dis. 2007 Jan 1;195(1):99-107
17152013
J Leukoc Biol. 2000 Oct;68(4):495-502
11037970
Immunology. 2009 Sep;128(1 Suppl):e766-76
19740338
Immunol Rev. 2000 Feb;173:39-51
10719666
Infect Immun. 2009 Feb;77(2):568-75
19015252
Curr Opin Infect Dis. 2009 Apr;22(2):102-8
19276877
J Infect Dis. 2006 Feb 1;193(3):370-9
16388484
Infect Immun. 2002 Mar;70(3):1372-81
11854223
Med Mycol. 2009;47(5):495-507
19048431
J Immunol. 2010 Mar 15;184(6):3079-86
20142364
Arterioscler Thromb Vasc Biol. 2007 Nov;27(11):2302-9
17717292
Am J Pathol. 2000 Jul;157(1):37-42
10880373
Infect Immun. 2006 Nov;74(11):6300-9
17000727
FASEB J. 1993 Dec;7(15):1475-82
8262332
Clin Infect Dis. 2007 Aug 1;45(3):308-14
17599307
Am J Respir Crit Care Med. 2003 May 15;167(10):1355-9
12574077
Clin Microbiol Rev. 2005 Apr;18(2):383-416
15831829
Immunity. 2004 Oct;21(4):539-50
15485631
Nat Rev Microbiol. 2006 Apr;4(4):272-82
16541135
Mol Microbiol. 2002 Nov;46(3):649-59
12410823
Intensive Care Med. 2008 Dec;34(12):2176-84
18807011
J Clin Invest. 2001 May;107(9):1055-61
11342566
Eur Respir J. 2010 Dec;36(6):1337-45
20378602
Immunol Cell Biol. 2001 Oct;79(5):490-501
11564157
PLoS One. 2008;3(10):e3494
18946505
J Infect Dis. 1999 Dec;180(6):1878-85
10558944
Am J Respir Cell Mol Biol. 2009 May;40(5):519-35
18978300
Infect Immun. 1996 Mar;64(3):782-90
8641782
Cytokine. 2005 May 21;30(4):203-11
15863395
Infect Immun. 2006 Apr;74(4):2423-7
16552072
Eur Respir J. 2003 Sep;22(3):542-50
14516149
J Infect Dis. 2008 Nov 1;198(9):1388-97
18855560