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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-U133B
52 Samples Loaded: 52
Human (Homo sapiens)
PBMC
Staphylococcus aureus
RNEasy Mini Kit
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample Title Age Gender Illness !Sample_title
GSM403283 PBMC S. aureus INF 109 HG-U133B 0.67y, when sample taken Female Bacteremia, Skin/Soft Tissue Abscess PBMC S. aureus INF 109 HG-U133B
GSM403285 PBMC Healthy Control INF 11N HG-U133B 4y, when sample taken Female None PBMC Healthy Control INF 11N HG-U133B
GSM403287 PBMC S. aureus INF 150 HG-U133B 9y, when sample taken Female Bacteremia, Osteomyelitis, Suppurative Arthritis, Myositis PBMC S. aureus INF 150 HG-U133B
GSM403289 PBMC S. aureus INF 179 HG-U133B 12y, when sample taken Male Bacteremia, Endocarditis, Emboli PBMC S. aureus INF 179 HG-U133B
GSM403291 PBMC S. aureus INF 205 HG-U133B 7y, when sample taken Male Bacteremia, Pneumonia, Skin/Soft Tissue Abscess PBMC S. aureus INF 205 HG-U133B
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File
Mod_GSE16129_GPL97_Grouping.csv
Sample Set Spreadsheet
Average Normalized
Raw Signal
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Sample ID !Sample Title Age Gender Illness !Sample Title Group Race Treatment Pathogen Array Sample ID
GSM403283
PBMC S. aureus INF 109 HG-U133B
0.67y, when sample taken
Female
Bacteremia, Skin/Soft Tissue Abscess
PBMC S. aureus INF 109 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006773
GSM403285
PBMC Healthy Control INF 11N HG-U133B
4y, when sample taken
Female
None
PBMC Healthy Control INF 11N HG-U133B
Healthy
Black
None
None
400006774
GSM403287
PBMC S. aureus INF 150 HG-U133B
9y, when sample taken
Female
Bacteremia, Osteomyelitis, Suppurative Arthritis, Myositis
PBMC S. aureus INF 150 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006775
GSM403289
PBMC S. aureus INF 179 HG-U133B
12y, when sample taken
Male
Bacteremia, Endocarditis, Emboli
PBMC S. aureus INF 179 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006776
GSM403291
PBMC S. aureus INF 205 HG-U133B
7y, when sample taken
Male
Bacteremia, Pneumonia, Skin/Soft Tissue Abscess
PBMC S. aureus INF 205 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006777
GSM403293
PBMC S. aureus INF 208 HG-U133B
10y, when sample taken
Female
Bacteremia, Osteomyelitis, CNS Abscess, Pneumonia, Emboli
PBMC S. aureus INF 208 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006778
GSM403295
PBMC S. aureus INF 216 HG-U133B
10y, when sample taken
Female
Bacteremia, Osteomyelitis
PBMC S. aureus INF 216 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006779
GSM403297
PBMC S. aureus INF 220 HG-U133B
11y, when sample taken
Male
Bacteremia, Osteomyelitis
PBMC S. aureus INF 220 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006780
GSM403299
PBMC S. aureus INF 221 HG-U133B
6y, when sample taken
Female
Bacteremia, Osteomyelitis
PBMC S. aureus INF 221 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006781
GSM403301
PBMC S. aureus INF 224 HG-U133B
10y, when sample taken
Male
Bacteremia, Osteomyelitis
PBMC S. aureus INF 224 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006782
GSM403303
PBMC S. aureus INF 230 HG-U133B
20y, when sample taken
Male
Bacteremia, Endocarditis, Skin/Soft Tissue Abscess
PBMC S. aureus INF 230 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006783
GSM403305
PBMC Healthy Control INF 23N HG-U133B
7y, when sample taken
Female
None
PBMC Healthy Control INF 23N HG-U133B
Healthy
Hispanic
None
None
400006784
GSM403307
PBMC S. aureus INF 24 HG-U133B
3y, when sample taken
Male
Bacteremia, Osteomyelitis, Myositis
PBMC S. aureus INF 24 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006785
GSM403309
PBMC S. aureus INF 241 HG-U133B
0.92y, when sample taken
Female
Bacteremia, Osteomyelitis, Pneumonia
PBMC S. aureus INF 241 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006786
GSM403311
PBMC S. aureus INF 242 HG-U133B
1.2y, when sample taken
Male
Bacteremia, Osteomyelitis, Pyomyositis
PBMC S. aureus INF 242 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006787
GSM403313
PBMC Healthy Control INF 24N HG-U133B
3y, when sample taken
Male
None
PBMC Healthy Control INF 24N HG-U133B
Healthy
White
None
None
400006788
GSM403315
PBMC S. aureus INF 258 HG-U133B
8y, when sample taken
Female
Bacteremia, Osteomyelitis, Cellulitis
PBMC S. aureus INF 258 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006789
GSM403317
PBMC S. aureus INF 262 HG-U133B
13y, when sample taken
Male
Bacteremia, Skin/Soft Tissue Abscess
PBMC S. aureus INF 262 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006790
GSM403319
PBMC S. aureus INF 264 HG-U133B
13y, when sample taken
Male
Bacteremia, Osteomyelitis, Suppurative Arthritis, Myositis, Skin/Soft Tissue Abscess, Emboli
PBMC S. aureus INF 264 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006791
GSM403321
PBMC S. aureus INF 271 HG-U133B
13y, when sample taken
Male
Osteomyelitis, Pyomyositis
PBMC S. aureus INF 271 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006792
GSM403323
PBMC Healthy Control INF 294 HG-U133B
12y, when sample taken
Female
None
PBMC Healthy Control INF 294 HG-U133B
Healthy
Black
None
None
400006793
GSM403325
PBMC S. aureus INF 30 HG-U133B
15y, when sample taken
Male
Bacteremia
PBMC S. aureus INF 30 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006794
GSM403327
PBMC Healthy Control INF 301 HG-U133B
8y, when sample taken
Male
None
PBMC Healthy Control INF 301 HG-U133B
Healthy
White
None
None
400006795
GSM403329
PBMC Healthy Control INF 303 HG-U133B
6y, when sample taken
Female
None
PBMC Healthy Control INF 303 HG-U133B
Healthy
White
None
None
400006796
GSM403331
PBMC Healthy Control INF 304 HG-U133B
6y, when sample taken
Male
None
PBMC Healthy Control INF 304 HG-U133B
Healthy
White
None
None
400006797
GSM403394
PBMC S. aureus INF 305 HG-U133B
4y, when sample taken
Female
Bacteremia, Osteomyelitis, Suppurative Arthritis
PBMC S. aureus INF 305 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006798
GSM403396
PBMC S. aureus INF 308 HG-U133B
12y, when sample taken
Female
Bacteremia, Pneumonia, Skin/Soft Tissue Abscess, Pyomyositis
PBMC S. aureus INF 308 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006799
GSM403398
PBMC S. aureus INF 328 HG-U133B
0.38y, when sample taken
Female
Bacteremia, Osteomyelitis, Pneumonia, Skin/Soft Tissue Abscess
PBMC S. aureus INF 328 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006800
GSM403400
PBMC S. aureus INF 329 HG-U133B
0.58y, when sample taken
Female
Bacteremia, Lymphadenitis
PBMC S. aureus INF 329 HG-U133B
S. aureus
Other
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006801
GSM403402
PBMC S. aureus INF 330 HG-U133B
11y, when sample taken
Female
Bacteremia, Pneumonia
PBMC S. aureus INF 330 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006802
GSM403404
PBMC S. aureus INF 354 HG-U133B
2y, when sample taken
Female
Bacteremia, Osteomyelitis
PBMC S. aureus INF 354 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006803
GSM403406
PBMC S. aureus INF 366 HG-U133B
11y, when sample taken
Female
Osteomyelitis, Skin/Soft Tissue Abscess
PBMC S. aureus INF 366 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006804
GSM403408
PBMC S. aureus INF 369 HG-U133B
14y, when sample taken
Male
Bacteremia, Suppurative arthritis, Skin/Soft Tissue Abscess, Emboli
PBMC S. aureus INF 369 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006805
GSM403410
PBMC S. aureus INF 372 HG-U133B
14y, when sample taken
Male
Bacteremia, Osteomyelitis, Myositis
PBMC S. aureus INF 372 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006806
GSM403412
PBMC Healthy Control INF 3N HG-U133B
6y, when sample taken
Male
None
PBMC Healthy Control INF 3N HG-U133B
Healthy
Hispanic
None
None
400006807
GSM403414
PBMC S. aureus INF 40 HG-U133B
13y, when sample taken
Male
Bacteremia, Osteomyelitis
PBMC S. aureus INF 40 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006808
GSM403416
PBMC S. aureus INF 412 HG-U133B
1.75y, when sample taken
Male
Bacteremia, Suppurative Arthritis
PBMC S. aureus INF 412 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006809
GSM403418
PBMC S. aureus INF 418 HG-U133B
8y, when sample taken
Female
Osteomyelitis
PBMC S. aureus INF 418 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006810
GSM403420
PBMC S. aureus INF 423 HG-U133B
8y, when sample taken
Male
Bacteremia, Osteomyelitis, Pyomyositis
PBMC S. aureus INF 423 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006811
GSM403422
PBMC S. aureus INF 43 HG-U133B
7y, when sample taken
Male
Bacteremia, Osteomyelitis, Pyomyositis, Suppurative Arthritis, Emboli
PBMC S. aureus INF 43 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006812
GSM403425
PBMC S. aureus INF 434 HG-U133B
5y, when sample taken
Male
Osteomyelitis, Pyomyositis
PBMC S. aureus INF 434 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006813
GSM403428
PBMC S. aureus INF 440 HG-U133B
0.5y, when sample taken
Male
Bacteremia, Osteomyelitis, Pneumonia, Emboli
PBMC S. aureus INF 440 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006814
GSM403430
PBMC S. aureus INF 450 HG-U133B
0.83y, when sample taken
Male
Bacteremia, Osteomyelitis, Suppurative Arthritis, Pyomyositis
PBMC S. aureus INF 450 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006815
GSM403434
PBMC S. aureus INF 451 HG-U133B
4y, when sample taken
Male
Bacteremia, Osteomyelitis, Suppurative Arthritis, Pyomyositis, Emboli
PBMC S. aureus INF 451 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006816
GSM403436
PBMC S. aureus INF 5 HG-U133B
10y, when sample taken
Male
Osteomyelitis
PBMC S. aureus INF 5 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006817
GSM403438
PBMC S. aureus INF 62 HG-U133B
2y, when sample taken
Male
Osteomyelitis, Pyomyositis
PBMC S. aureus INF 62 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006818
GSM403440
PBMC S. aureus INF 66 HG-U133B
0.25y, when sample taken
Female
Pneumonia
PBMC S. aureus INF 66 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006819
GSM403442
PBMC S. aureus INF 67 HG-U133B
7y, when sample taken
Female
Bacteremia, Osteomyelitis
PBMC S. aureus INF 67 HG-U133B
S. aureus
White
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006820
GSM403547
PBMC Healthy Control INF 7N HG-U133B
1.6y, when sample taken
Female
None
PBMC Healthy Control INF 7N HG-U133B
Healthy
Black
None
None
400006821
GSM403549
PBMC S. aureus INF 88 HG-U133B
0.92y, when sample taken
Male
Bacteremia, Osteomyelitis, Pneumonia, Emboli
PBMC S. aureus INF 88 HG-U133B
S. aureus
Hispanic
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-resistant
400006822
GSM403552
PBMC Healthy Control INF 8N HG-U133B
10y, when sample taken
Male
None
PBMC Healthy Control INF 8N HG-U133B
Healthy
Black
None
None
400006823
GSM403554
PBMC S. aureus INF 90 HG-U133B
0.67y, when sample taken
Male
Bacteremia, Suppurative arthritis
PBMC S. aureus INF 90 HG-U133B
S. aureus
Black
Anti-staphylococcal antibiotic
Staphylococcus aureus, methicillin-susceptible
400006824

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