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Host Immune Transcriptional Profiles Reflect the Variability in Clinical Disease Manifestations in Patients with Staphylococcus aureus Infections

Author

Listed:
  • Romain Banchereau
  • Alejandro Jordan-Villegas
  • Monica Ardura
  • Asuncion Mejias
  • Nicole Baldwin
  • Hui Xu
  • Elizabeth Saye
  • Jose Rossello-Urgell
  • Phuong Nguyen
  • Derek Blankenship
  • Clarence B Creech
  • Virginia Pascual
  • Jacques Banchereau
  • Damien Chaussabel
  • Octavio Ramilo

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.

Suggested Citation

  • Romain Banchereau & Alejandro Jordan-Villegas & Monica Ardura & Asuncion Mejias & Nicole Baldwin & Hui Xu & Elizabeth Saye & Jose Rossello-Urgell & Phuong Nguyen & Derek Blankenship & Clarence B Creec, 2012. "Host Immune Transcriptional Profiles Reflect the Variability in Clinical Disease Manifestations in Patients with Staphylococcus aureus Infections," PLOS ONE, Public Library of Science, vol. 7(4), pages 1-11, April.
    • Handle: RePEc:plo:pone00:0034390
    DOI: 10.1371/journal.pone.0034390
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    References listed on IDEAS

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    1. Matthew P. R. Berry & Christine M. Graham & Finlay W. McNab & Zhaohui Xu & Susannah A. A. Bloch & Tolu Oni & Katalin A. Wilkinson & Romain Banchereau & Jason Skinner & Robert J. Wilkinson & Charles Qu, 2010. "An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis," Nature, Nature, vol. 466(7309), pages 973-977, August.
    2. Chao Chen & Kay Grennan & Judith Badner & Dandan Zhang & Elliot Gershon & Li Jin & Chunyu Liu, 2011. "Removing Batch Effects in Analysis of Expression Microarray Data: An Evaluation of Six Batch Adjustment Methods," PLOS ONE, Public Library of Science, vol. 6(2), pages 1-10, February.
    3. Sugar, Catherine A. & James, Gareth M., 2003. "Finding the Number of Clusters in a Dataset: An Information-Theoretic Approach," Journal of the American Statistical Association, American Statistical Association, vol. 98, pages 750-763, January.
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