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, Steven A. Porcelli, D. D. Fraser, C. M. Martin, I. Welch, T. Mele, S. M M Haeryfar, J. K. Mccormick

Research output: Contribution to journalArticle

8 Citations (Scopus)

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

Fingerprint

Natural Killer T-Cells
Sepsis
Cytokines
Mortality
Anti-Inflammatory Agents
T-Lymphocytes
Interleukin-13
Interleukin-17
Natural Killer Cells
B-Lymphocytes
Spleen
Macrophages
Lymphocytes
Apoptosis
Morbidity
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis. / Anantha, R. V.; Mazzuca, D. M.; Xu, S. X.; Porcelli, Steven A.; Fraser, D. D.; Martin, C. M.; Welch, I.; Mele, T.; Haeryfar, S. M M; Mccormick, J. K.

In: Clinical and Experimental Immunology, Vol. 178, No. 2, 01.11.2014, p. 292-309.

Research output: Contribution to journalArticle

Anantha, RV, Mazzuca, DM, Xu, SX, Porcelli, SA, Fraser, DD, Martin, CM, Welch, I, Mele, T, Haeryfar, SMM & Mccormick, JK 2014, 'T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis', Clinical and Experimental Immunology, vol. 178, no. 2, pp. 292-309. https://doi.org/10.1111/cei.12404
Anantha, R. V. ; Mazzuca, D. M. ; Xu, S. X. ; Porcelli, Steven A. ; Fraser, D. D. ; Martin, C. M. ; Welch, I. ; Mele, T. ; Haeryfar, S. M M ; Mccormick, J. K. / T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis. In: Clinical and Experimental Immunology. 2014 ; Vol. 178, No. 2. pp. 292-309.
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