T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis

R. V. Anantha, D. M. Mazzuca, S. X. Xu, S. A. Porcelli, D. D. Fraser, C. M. Martin, I. Welch, T. Mele, S. M.M. Haeryfar, J. K. Mccormick

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Summary: Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNKT) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNKT cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNKT cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNKT cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNKT cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNKT cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis.

Original languageEnglish (US)
Pages (from-to)292-309
Number of pages18
JournalClinical and Experimental Immunology
Volume178
Issue number2
DOIs
StatePublished - Nov 1 2014

Keywords

  • Acute intra-abdominal sepsis
  • Glycolipids
  • Invariant natural killer T cells
  • Th2 response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Anantha, R. V., Mazzuca, D. M., Xu, S. X., Porcelli, S. A., Fraser, D. D., Martin, C. M., Welch, I., Mele, T., Haeryfar, S. M. M., & Mccormick, J. K. (2014). T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis. Clinical and Experimental Immunology, 178(2), 292-309. https://doi.org/10.1111/cei.12404