Interleukin-7 (IL-7) treatment accelerates neutrophil recruitment through γδ T-cell IL-17 production in a murine model of sepsis

Kevin R. Kasten, Priya S. Prakash, Jacqueline Unsinger, Holly S. Goetzman, Lisa G. England, Cindy M. Cave, Aaron P. Seitz, Cristina N. Mazuski, Tony T. Zhou, Michel Morre, Richard S. Hotchkiss, David A. Hildeman, Charles C. Caldwell

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

The sepsis syndrome represents an improper immune response to infection and is associated with unacceptably high rates of mortality and morbidity. The interactions between T cells and the innate immune system while combating sepsis are poorly understood. In this report, we observed that treatment with the potent, antiapoptotic cytokine interleukin-7 (IL-7) accelerated neutrophil recruitment and improved bacterial clearance. We first determined that T cells were necessary for the previously observed IL-7-mediated enhanced survival. Next, IL-7 increased Bcl-2 expression in T cells isolated from septic mice as early as 3 h following treatment. This treatment resulted in increased gamma interferon (IFN-γ) and IP-10 production within the septic peritoneum together with local and systemic increases of IL-17 in IL-7-treated mice. We further demonstrate that the increase in IL-17 was largely due to increased recruitment and production by γδ T cells, which express CXCR3. Consistent with increased IL-17 production, IL-7 treatment increased CXCL1/KC production, neutrophil recruitment, and bacterial clearance. Significantly, end-organ tissue injury was not significantly different between vehicle- and IL-7-treated mice. Collectively, these data illustrate that IL-7 can mediate the cross talk between Th1 and Th17 lymphocytes during sepsis such that neutrophil recruitment and bacterial clearance is improved while early tissue injury is not increased. All together, these observations may underlay novel potential therapeutic targets to improve the host immune response to sepsis.

Original languageEnglish
Pages (from-to)4714-4722
Number of pages9
JournalInfection and immunity
Volume78
Issue number11
DOIs
StatePublished - Nov 2010

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    Kasten, K. R., Prakash, P. S., Unsinger, J., Goetzman, H. S., England, L. G., Cave, C. M., Seitz, A. P., Mazuski, C. N., Zhou, T. T., Morre, M., Hotchkiss, R. S., Hildeman, D. A., & Caldwell, C. C. (2010). Interleukin-7 (IL-7) treatment accelerates neutrophil recruitment through γδ T-cell IL-17 production in a murine model of sepsis. Infection and immunity, 78(11), 4714-4722. https://doi.org/10.1128/IAI.00456-10