Cancer Institute A national cancer institute
designated cancer center

Christopher H. Contag

Publication Details

  • The T Cell STAT Signaling Network Is Reprogrammed within Hours of Bacteremia via Secondary Signals JOURNAL OF IMMUNOLOGY Hotson, A. N., Hardy, J. W., Hale, M. B., Contag, C. H., Nolan, G. P. 2009; 182 (12): 7558-7568


    The delicate balance between protective immunity and inflammatory disease is challenged during sepsis, a pathologic state characterized by aspects of both a hyperactive immune response and immunosuppression. The events driven by systemic infection by bacterial pathogens on the T cell signaling network that likely control these responses have not been illustrated in great detail. We characterized how intracellular signaling within the immune compartment is reprogrammed at the single cell level when the host is challenged with a high level of pathogen. To accomplish this, we applied flow cytometry to measure the phosphorylation potential of key signal transduction proteins during acute bacterial challenge. We modeled the onset of sepsis by i.v. administration of avirulent strains of Listeria monocytogenes and Escherichia coli to mice. Within 6 h of bacterial challenge, T cells were globally restricted in their ability to respond to specific cytokine stimulations as determined by assessing the extent of STAT protein phosphorylation. Mechanisms by which this negative feedback response occurred included SOCS1 and SOCS3 gene up-regulation and IL-6-induced endocystosis of the IL-6 receptor. Additionally, macrophages were partially tolerized in their ability to respond to TLR agonists. Thus, in contrast to the view that there is a wholesale immune activation during sepsis, one immediate host response to blood-borne bacteria was induction of a refractory period during which leukocyte activation by specific stimulations was attenuated.

    View details for DOI 10.4049/jimmunol.0803666

    View details for Web of Science ID 000266833900026

    View details for PubMedID 19494279

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