Enhanced monocyte response and decreased central memory T cells in children with invasive Staphylococcus aureus infections.
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.
Division of Pediatric Infectious Disease, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Monica I
MI
Ardura
Romain
R
Banchereau
Asuncion
A
Mejias
Tiziana
T
Di Pucchio
Casey
C
Glaser
Florence
F
Allantaz
Virginia
V
Pascual
Jacques
J
Banchereau
Damien
D
Chaussabel
Octavio
O
Ramilo
D000208:Acute Disease; D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D016022:Case-Control Studies; D002451:Cell Compartmentation; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D003710:Demography; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D015203:Reproducibility of Results; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology*