title: Host immune transcriptional profiles reflect the variability in clinical disease manifestations in patients with Staphylococcus aureus infections.
abstract: Staphylococcus aureus infections are associated with diverse clinical manifestations leading to significant morbidity and mortality. To define the role of the host response in the clinical manifestations of the disease, we characterized whole blood transcriptional profiles of children hospitalized with community-acquired S. aureus infection and phenotyped the bacterial strains isolated. The overall transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis related genes and under-expression of genes related to adaptive immunity. We assessed individual profiles using modular fingerprints combined with the molecular distance to health (MDTH), a numerical score of transcriptional perturbation as compared to healthy controls. We observed significant heterogeneity in the host signatures and MDTH, as they were influenced by the type of clinical presentation, the extent of bacterial dissemination, and time of blood sampling in the course of the infection, but not by the bacterial isolate. System analysis approaches provide a new understanding of disease pathogenesis and the relation/interaction between host response and clinical disease manifestations.
authors.affiliation: UT Southwestern Medical Center, Dallas, Texas, United States of America. romain.banchereau@utsouthwestern.edu
authors.forename: Romain
authors.initials: R
authors.lastname: Banchereau
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jordan-Villegas
authors.forename: Monica
authors.initials: M
authors.lastname: Ardura
authors.forename: Asuncion
authors.initials: A
authors.lastname: Mejias
authors.forename: Nicole
authors.initials: N
authors.lastname: Baldwin
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Saye
authors.forename: Jose
authors.initials: J
authors.lastname: Rossello-Urgell
authors.forename: Phuong
authors.initials: P
authors.lastname: Nguyen
authors.forename: Derek
authors.initials: D
authors.lastname: Blankenship
authors.forename: Clarence B
authors.initials: CB
authors.lastname: Creech
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
authors.forename: Octavio
authors.initials: O
authors.lastname: Ramilo
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007223:Infant; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D013203:Staphylococcal Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification
chemical_list: D015415:Biomarkers; D001798:Blood Proteins