期刊
PLOS ONE
卷 4, 期 5, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0005446
关键词
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资金
- NCI NIH HHS [P01 CA084512, R01 CA078846] Funding Source: Medline
- NCRR NIH HHS [UL1RR024982, KL2 RR024983, UL1 RR024982, KL2RR024983] Funding Source: Medline
- NIAID NIH HHS [U19 AI057234] Funding Source: Medline
- NIAMS NIH HHS [P50 AR054083, R01 AR050770-01, R01 AR050770] Funding Source: Medline
- PHS HHS [U19 AIO57234-02, R01 I068842] Funding Source: Medline
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 numbers 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.
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