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Clinical

Enhanced Monocyte Response & Decreased Central Memory T Cells in Children with Invasive Staphylococcus aureus Infections

Purpose

Staphylococcus aureus has emerged as a significant pathogen causing severe, invasive disease in otherwise healthy people. Despite considerable advances in understanding the epidemiology, resistance mechanisms, and virulence factors produced by the bacteria, there is limited knowledge of the in vivo host immune response to acute, invasive S. aureus infections. Herein, we report that peripheral blood mononuclear cells from patients with severe S. aureus infections demonstrate a distinctive and robust gene expression profile which is validated in a distinct group of patients and on a different microarray platform. Application of a systems-wide modular analysis framework reveals significant over-expression of innate immunity genes and under-expression of genes related to adaptive immunity. Simultaneous flow cytometry analyses demonstrated marked alterations in immune cell numbers, with decreased central memory CD4 and CD8 T cells and increased number of monocytes. CD14+ monocyte numbers significantly correlated with the gene expression levels of genes related to the innate immune response. These results demonstrate the value of applying a systems biology approach that reveals the significant alterations in the components of circulating blood lymphocytes and monocytes in invasive S. aureus infections.

Hypothesis

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Experimental Design

Blood samples were collected from patients with S. aureus infections and healthy controls. 108 Affymetrix and 18 Illumina arrays.

Experimental Variables

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Controls

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Methods

The data were analyzed with Microarray Suite version 5.0 (MAS 5.0) using Affymetrix default analysis settings and global scaling as normalization method. The trimmed mean target intensity of each array was arbitrarily set to 500.

Additional Information

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16129

Microarray
Affymetrix HG-U133A
56 Samples Loaded: 56
Human (Homo sapiens)
PBMC
Staphylococcus aureus
RNEasy Mini Kit
Sample Set Spreadsheet
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Samples Preview
Sample ID Age Gender Illness !Sample_title group
GSM403282 0.67y, when sample taken Female Bacteremia, Skin/Soft Tissue Abscess PBMC S. aureus INF 109 HG-U133A S. aureus
GSM403284 4y, when sample taken Female None PBMC Healthy Control INF 11N HG-U133A Healthy
GSM403286 9y, when sample taken Female Bacteremia, Osteomyelitis, Suppurative Arthritis, Myositis PBMC S. aureus INF 150 HG-U133A S. aureus
GSM403288 12y, when sample taken Male Bacteremia, Endocarditis, Emboli PBMC S. aureus INF 179 HG-U133A S. aureus
GSM403290 7y, when sample taken Male Bacteremia, Pneumonia, Skin/Soft Tissue Abscess PBMC S. aureus INF 205 HG-U133A S. aureus
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File
Mod_GSE16129_GPL96_Grouping.csv
Sample Set Spreadsheet
Raw Signal
Raw Signal
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Samples Viewer / Editor

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Sample ID Age Gender Illness !Sample Title Group Race Treatment Pathogen Sample Title Array Sample ID
GSM403282
0.67y, when sample taken
Female
Bacteremia, Skin/Soft Tissue Abscess
PBMC S. aureus INF 109 HG-U133A
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 109 HG-U133A
400006717
GSM403284
4y, when sample taken
Female
None
PBMC Healthy Control INF 11N HG-U133A
Healthy
Black
None
None
PBMC Healthy Control INF 11N HG-U133A
400006718
GSM403286
9y, when sample taken
Female
Bacteremia, Osteomyelitis, Suppurative Arthritis, Myositis
PBMC S. aureus INF 150 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 150 HG-U133A
400006719
GSM403288
12y, when sample taken
Male
Bacteremia, Endocarditis, Emboli
PBMC S. aureus INF 179 HG-U133A
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 179 HG-U133A
400006720
GSM403290
7y, when sample taken
Male
Bacteremia, Pneumonia, Skin/Soft Tissue Abscess
PBMC S. aureus INF 205 HG-U133A
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 205 HG-U133A
400006721
GSM403292
10y, when sample taken
Female
Bacteremia, Osteomyelitis, CNS Abscess, Pneumonia, Emboli
PBMC S. aureus INF 208 HG-U133A
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 208 HG-U133A
400006722
GSM403294
10y, when sample taken
Female
Bacteremia, Osteomyelitis
PBMC S. aureus INF 216 HG-U133A
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 216 HG-U133A
400006723
GSM403296
11y, when sample taken
Male
Bacteremia, Osteomyelitis
PBMC S. aureus INF 220 HG-U133A
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 220 HG-U133A
400006724
GSM403298
6y, when sample taken
Female
Bacteremia, Osteomyelitis
PBMC S. aureus INF 221 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 221 HG-U133A
400006725
GSM403300
10y, when sample taken
Male
Bacteremia, Osteomyelitis
PBMC S. aureus INF 224 HG-U133A
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 224 HG-U133A
400006726
GSM403302
20y, when sample taken
Male
Bacteremia, Endocarditis, Skin/Soft Tissue Abscess
PBMC S. aureus INF 230 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 230 HG-U133A
400006727
GSM403304
7y, when sample taken
Female
None
PBMC Healthy Control INF 23N HG-U133A
Healthy
Hispanic
None
None
PBMC Healthy Control INF 23N HG-U133A
400006728
GSM403306
3y, when sample taken
Male
Bacteremia, Osteomyelitis, Myositis
PBMC S. aureus INF 24 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 24 HG-U133A
400006729
GSM403308
0.92y, when sample taken
Female
Bacteremia, Osteomyelitis, Pneumonia
PBMC S. aureus INF 241 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 241 HG-U133A
400006730
GSM403310
1.2y, when sample taken
Male
Bacteremia, Osteomyelitis, Pyomyositis
PBMC S. aureus INF 242 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 242 HG-U133A
400006731
GSM403312
3y, when sample taken
Male
None
PBMC Healthy Control INF 24N HG-U133A
Healthy
White
None
None
PBMC Healthy Control INF 24N HG-U133A
400006732
GSM403314
8y, when sample taken
Female
Bacteremia, Osteomyelitis, Cellulitis
PBMC S. aureus INF 258 HG-U133A
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 258 HG-U133A
400006733
GSM403316
13y, when sample taken
Male
Bacteremia, Skin/Soft Tissue Abscess
PBMC S. aureus INF 262 HG-U133A
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 262 HG-U133A
400006734
GSM403318
13y, when sample taken
Male
Bacteremia, Osteomyelitis, Suppurative Arthritis, Myositis, Skin/Soft Tissue Abscess, Emboli
PBMC S. aureus INF 264 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 264 HG-U133A
400006735
GSM403320
13y, when sample taken
Male
Osteomyelitis, Pyomyositis
PBMC S. aureus INF 271 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 271 HG-U133A
400006736
GSM403322
12y, when sample taken
Female
None
PBMC Healthy Control INF 294 HG-U133A
Healthy
Black
None
None
PBMC Healthy Control INF 294 HG-U133A
400006737
GSM403324
15y, when sample taken
Male
Bacteremia
PBMC S. aureus INF 30 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 30 HG-U133A
400006738
GSM403326
8y, when sample taken
Male
None
PBMC Healthy Control INF 301 HG-U133A
Healthy
White
None
None
PBMC Healthy Control INF 301 HG-U133A
400006739
GSM403328
6y, when sample taken
Female
None
PBMC Healthy Control INF 303 HG-U133A
Healthy
White
None
None
PBMC Healthy Control INF 303 HG-U133A
400006740
GSM403330
6y, when sample taken
Male
None
PBMC Healthy Control INF 304 HG-U133A
Healthy
White
None
None
PBMC Healthy Control INF 304 HG-U133A
400006741
GSM403393
4y, when sample taken
Female
Bacteremia, Osteomyelitis, Suppurative Arthritis
PBMC S. aureus INF 305 HG-U133A
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 305 HG-U133A
400006742
GSM403395
12y, when sample taken
Female
Bacteremia, Pneumonia, Skin/Soft Tissue Abscess, Pyomyositis
PBMC S. aureus INF 308 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 308 HG-U133A
400006743
GSM403397
0.38y, when sample taken
Female
Bacteremia, Osteomyelitis, Pneumonia, Skin/Soft Tissue Abscess
PBMC S. aureus INF 328 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 328 HG-U133A
400006744
GSM403399
0.58y, when sample taken
Female
Bacteremia, Lymphadenitis
PBMC S. aureus INF 329 HG-U133A
S. aureus
Other
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 329 HG-U133A
400006745
GSM403401
11y, when sample taken
Female
Bacteremia, Pneumonia
PBMC S. aureus INF 330 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 330 HG-U133A
400006746
GSM403403
2y, when sample taken
Female
Bacteremia, Osteomyelitis
PBMC S. aureus INF 354 HG-U133A
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 354 HG-U133A
400006747
GSM403405
11y, when sample taken
Female
Osteomyelitis, Skin/Soft Tissue Abscess
PBMC S. aureus INF 366 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 366 HG-U133A
400006748
GSM403407
14y, when sample taken
Male
Bacteremia, Suppurative arthritis, Skin/Soft Tissue Abscess, Emboli
PBMC S. aureus INF 369 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 369 HG-U133A
400006749
GSM403409
14y, when sample taken
Male
Bacteremia, Osteomyelitis, Myositis
PBMC S. aureus INF 372 HG-U133A
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 372 HG-U133A
400006750
GSM403411
6y, when sample taken
Male
None
PBMC Healthy Control INF 3N HG-U133A
Healthy
Hispanic
None
None
PBMC Healthy Control INF 3N HG-U133A
400006751
GSM403413
13y, when sample taken
Male
Bacteremia, Osteomyelitis
PBMC S. aureus INF 40 HG-U133A
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 40 HG-U133A
400006752
GSM403415
1.75y, when sample taken
Male
Bacteremia, Suppurative Arthritis
PBMC S. aureus INF 412 HG-U133A
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 412 HG-U133A
400006753
GSM403417
8y, when sample taken
Female
Osteomyelitis
PBMC S. aureus INF 418 HG-U133A
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 418 HG-U133A
400006754
GSM403419
8y, when sample taken
Male
Bacteremia, Osteomyelitis, Pyomyositis
PBMC S. aureus INF 423 HG-U133A
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 423 HG-U133A
400006755
GSM403421
7y, when sample taken
Male
Bacteremia, Osteomyelitis, Pyomyositis, Suppurative Arthritis, Emboli
PBMC S. aureus INF 43 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 43 HG-U133A
400006756
GSM403423
5y, when sample taken
Male
Osteomyelitis, Pyomyositis
PBMC S. aureus INF 434 HG-U133A j5582087g
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 434 HG-U133A j5582087g
400006757
GSM403424
5y, when sample taken
Male
Osteomyelitis, Pyomyositis
PBMC S. aureus INF 434 HG-U133A j7304007g
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 434 HG-U133A j7304007g
400006758
GSM403426
0.5y, when sample taken
Male
Bacteremia, Osteomyelitis, Pneumonia, Emboli
PBMC S. aureus INF 440 HG-U133A j4437174g
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 440 HG-U133A j4437174g
400006759
GSM403427
0.5y, when sample taken
Male
Bacteremia, Osteomyelitis, Pneumonia, Emboli
PBMC S. aureus INF 440 HG-U133A j7876570g
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 440 HG-U133A j7876570g
400006760
GSM403429
0.83y, when sample taken
Male
Bacteremia, Osteomyelitis, Suppurative Arthritis, Pyomyositis
PBMC S. aureus INF 450 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 450 HG-U133A
400006761
GSM403431
4y, when sample taken
Male
Bacteremia, Osteomyelitis, Suppurative Arthritis, Pyomyositis, Emboli
PBMC S. aureus INF 451 HG-U133A j1806278g
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 451 HG-U133A j1806278g
400006762
GSM403432
4y, when sample taken
Male
Bacteremia, Osteomyelitis, Suppurative Arthritis, Pyomyositis, Emboli
PBMC S. aureus INF 451 HG-U133A j2985113g
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 451 HG-U133A j2985113g
400006763
GSM403433
4y, when sample taken
Male
Bacteremia, Osteomyelitis, Suppurative Arthritis, Pyomyositis, Emboli
PBMC S. aureus INF 451 HG-U133A j4288324g
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 451 HG-U133A j4288324g
400006764
GSM403435
10y, when sample taken
Male
Osteomyelitis
PBMC S. aureus INF 5 HG-U133A
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 5 HG-U133A
400006765
GSM403437
2y, when sample taken
Male
Osteomyelitis, Pyomyositis
PBMC S. aureus INF 62 HG-U133A
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 62 HG-U133A
400006766
GSM403439
0.25y, when sample taken
Female
Pneumonia
PBMC S. aureus INF 66 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 66 HG-U133A
400006767
GSM403441
7y, when sample taken
Female
Bacteremia, Osteomyelitis
PBMC S. aureus INF 67 HG-U133A
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 67 HG-U133A
400006768
GSM403546
1.6y, when sample taken
Female
None
PBMC Healthy Control INF 7N HG-U133A
Healthy
Black
None
None
PBMC Healthy Control INF 7N HG-U133A
400006769
GSM403548
0.92y, when sample taken
Male
Bacteremia, Osteomyelitis, Pneumonia, Emboli
PBMC S. aureus INF 88 HG-U133A
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
PBMC S. aureus INF 88 HG-U133A
400006770
GSM403551
10y, when sample taken
Male
None
PBMC Healthy Control INF 8N HG-U133A
Healthy
Black
None
None
PBMC Healthy Control INF 8N HG-U133A
400006771
GSM403553
0.67y, when sample taken
Male
Bacteremia, Suppurative arthritis
PBMC S. aureus INF 90 HG-U133A
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
PBMC S. aureus INF 90 HG-U133A
400006772

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