Large scale immune profiling of infected humans and goats reveals differential recognition of Brucella melitensis antigens.
Brucellosis is a widespread zoonotic disease that is also a potential agent of bioterrorism. Current serological assays to diagnose human brucellosis in clinical settings are based on detection of agglutinating anti-LPS antibodies. To better understand the universe of antibody responses that develop after B. melitensis infection, a protein microarray was fabricated containing 1,406 predicted B. melitensis proteins. The array was probed with sera from experimentally infected goats and naturally infected humans from an endemic region in Peru. The assay identified 18 antigens differentially recognized by infected and non-infected goats, and 13 serodiagnostic antigens that differentiate human patients proven to have acute brucellosis from syndromically similar patients. There were 31 cross-reactive antigens in healthy goats and 20 cross-reactive antigens in healthy humans. Only two of the serodiagnostic antigens and eight of the cross-reactive antigens overlap between humans and goats. Based on these results, a nitrocellulose line blot containing the human serodiagnostic antigens was fabricated and applied in a simple assay that validated the accuracy of the protein microarray results in the diagnosis of humans. These data demonstrate that an experimentally infected natural reservoir host produces a fundamentally different immune response than a naturally infected accidental human host.
Liang
Li
L
Division of Infectious Diseases, Department of Medicine, University of California Irvine, Irvine, California, USA.
Leng
Diana
D
Burk
Chad
C
Nakajima-Sasaki
Rie
R
Kayala
Matthew A
MA
Atluri
Vidya L
VL
Pablo
Jozelyn
J
Unal
Berkay
B
Ficht
Thomas A
TA
Gotuzzo
Eduardo
E
Saito
Mayuko
M
Morrow
W John W
WJ
Liang
Xiaowu
X
Baldi
Pierre
P
Gilman
Robert H
RH
Vinetz
Joseph M
JM
Tsolis
Renée M
RM
Felgner
Philip L
PL
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D017347:Brucella melitensis / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology* / Q000662:veterinary*; D003429:Cross Reactions; D019353:Endemic Diseases / Q000662:veterinary; D015511:Goat Diseases / Q000276:immunology*; D006041:Goats; D006801:Humans; D007118:Immunoassay / Q000379:methods; D010568:Peru; D040081:Protein Array Analysis
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial
Clin Diagn Lab Immunol. 2002 Mar;9(2):366-9
11874879
Infect Immun. 1996 Jul;64(7):2490-9
8698471
Infect Immun. 2005 Nov;73(11):7297-303
16239526
Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):547-52
15647345
J Infect. 2004 Aug;49(2):102-8
15236916
Clin Vaccine Immunol. 2008 Jun;15(6):911-5
18385457
Vet Rec. 1969 Dec 6;85(23):636-41
5358072
Genome Biol. 2005;6(2):R16
15693945
Lancet Infect Dis. 2007 Dec;7(12):775-86
18045560
Clin Diagn Lab Immunol. 1997 Sep;4(5):556-64
9302205
Bioinformatics. 2004 Sep 1;20(13):2026-34
15044229
Bioinformatics. 2007 Feb 15;23(4):487-92
17204462
Neural Comput. 1998 Jul 28;10(6):1455-80
9698353
J Vet Diagn Invest. 2002 Sep;14(5):407-11
12296393
Vet Microbiol. 2003 May 19;93(2):101-7
12636998
Gene. 1988;63(1):1-9
3133283
J Clin Microbiol. 1994 May;32(5):1159-65
8051240
J Comput Biol. 2000;7(6):805-17
11382363
Infect Immun. 1994 Mar;62(3):1000-7
8112833
J Proteome Res. 2009 Mar;8(3):1594-609
19216536
N Engl J Med. 2005 Jun 2;352(22):2325-36
15930423
Clin Infect Dis. 1995 Aug;21(2):283-9; quiz 290
8562733
Bioinformatics. 2002;18 Suppl 1:S96-104
12169536
J Clin Microbiol. 2009 Oct;47(10):3147-55
19656979
Proteomics. 2008 Nov;8(22):4680-94
18937256
Trans R Soc Trop Med Hyg. 2009 Apr;103(4):399-402
19027131
Lancet Infect Dis. 2006 Feb;6(2):91-9
16439329
Comp Immunol Microbiol Infect Dis. 2010 Sep;33(5):435-42
19625085
Epidemiol Infect. 1992 Feb;108(1):77-85
1547843
Vaccine. 2006 Jun 12;24(24):5169-77
16697090
Proteomics. 2007 May;7(10):1678-86
17443847
Am J Trop Med Hyg. 2008 Apr;78(4):595-8
18385354
J Clin Microbiol. 2000 Nov;38(11):4000-5
11060059
Proteomics. 2006 Jul;6(13):3767-80
16739129
FEMS Immunol Med Microbiol. 1994 Jan;8(1):49-56
8156050
Infect Immun. 1995 Apr;63(4):1409-14
7890403
Proteomics. 2008 Sep;8(18):3862-70
18704908
Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13499-504
19666533
Diagn Microbiol Infect Dis. 2006 May;55(1):27-35
16500069
FEMS Immunol Med Microbiol. 2006 Nov;48(2):252-6
17064279
Infect Immun. 2008 Aug;76(8):3374-89
18474646
J Clin Microbiol. 1982 Oct;16(4):756-7
7153327
J Clin Microbiol. 1992 Mar;30(3):604-7
1551977
Bioinformatics. 2007 Jul 1;23(13):i508-18
17646338
Stat Med. 1990 Jul;9(7):811-8
2218183
Nucleic Acids Res. 2009 Feb;37(2):e17
19103660
Infect Immun. 1982 Mar;35(3):979-89
6802764
Bioinformatics. 2001 Jun;17(6):509-19
11395427
FEMS Microbiol Lett. 1996 Jul 1;140(2-3):139-44
8764475
Curr Opin Microbiol. 2003 Dec;6(6):586-93
14662354
Trans R Soc Trop Med Hyg. 2007 Jul;101(7):707-13
17442354
Clin Vaccine Immunol. 2008 Jun;15(6):1031-3
18448622
Clin Lab. 2003;49(11-12):577-89
14651329
Vet Immunol Immunopathol. 2008 Jun 15;123(3-4):223-9
18359093
Biochim Biophys Acta. 1992 Feb 28;1130(1):120-2
1347461
BMC Bioinformatics. 2006 Dec 15;7:533
17173684
Clin Vaccine Immunol. 2008 Feb;15(2):208-14
18077620
Bioinformatics. 2006 Jul 15;22(14):1760-6
16644788
Clin Infect Dis. 1996 Mar;22(3):446-55
8852961
Am J Trop Med Hyg. 2009 Apr;80(4):625-7
19346389
Dev Biol Stand. 1984;56:341-8
6489620
Clin Diagn Lab Immunol. 1996 May;3(3):305-8
8705674
Clin Diagn Lab Immunol. 2004 Jan;11(1):111-4
14715555
J Clin Microbiol. 1996 Jan;34(1):165-9
8748294
Infect Immun. 1994 Sep;62(9):3633-9
8063379
Bioinformatics. 2002;18 Suppl 1:S105-10
12169537