NK but not CD1-restricted NKT cells facilitate systemic inflammation during polymicrobial intra-abdominal sepsis

Anthony O. Etogo, Jesus Nunez, Cheng Y. Lin, Tracy Toliver-Kinsky, Edward R. Sherwood

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Abstract

Evidence suggests that NK and NKT cells contribute to inflammation and mortality during septic shock caused by cecal ligation and puncture (CLP). However, the specific contributions of these cell types to the pathogenesis of CLP-induced septic shock have not been fully defined. The goal of the present study was to determine the mechanisms by which NK and NKT cells mediate the host response to CLP. Control, NK cell-deficient, and NKT cell-deficient mice underwent CLP. Survival, cytokine production, and bacterial clearance were measured. NK cell trafficking and interaction with myeloid cells was also studied. Results show that mice treated with anti-asialoGM1 (NK cell deficient) or anti-NK1.1 (NK/NKT cell deficient) show less systemic inflammation and have improved survival compared with IgG-treated controls. CD1 knockout mice (NKT cell deficient) did not demonstrate decreased cytokine production or improved survival compared with wild type mice. Trafficking studies show migration of NK cells from blood and spleen into the inflamed peritoneal cavity where they appear to facilitate the activation of peritoneal macrophages (F4-80 +GR-1-) and F4-80+Gr-1+ myeloid cells. These findings indicate that NK but not CD1-restricted NKT cells contribute to acute CLP-induced inflammation. NK cells appear to mediate their proinflammatory functions during septic shock, in part, by migration into the peritoneal cavity and amplification of the proinflammatory activities of specific myeloid cell populations. These findings provide new insights into the mechanisms used by NK cells to facilitate acute inflammation during septic shock.

Original languageEnglish (US)
Pages (from-to)6334-6345
Number of pages12
JournalJournal of Immunology
Volume180
Issue number9
StatePublished - May 1 2008

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Natural Killer T-Cells
Natural Killer Cells
Sepsis
Inflammation
Punctures
Ligation
Septic Shock
Myeloid Cells
Peritoneal Cavity
Cytokines
Peritoneal Macrophages
Knockout Mice
Cell Communication
Spleen
Immunoglobulin G
Mortality

ASJC Scopus subject areas

  • Immunology

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NK but not CD1-restricted NKT cells facilitate systemic inflammation during polymicrobial intra-abdominal sepsis. / Etogo, Anthony O.; Nunez, Jesus; Lin, Cheng Y.; Toliver-Kinsky, Tracy; Sherwood, Edward R.

In: Journal of Immunology, Vol. 180, No. 9, 01.05.2008, p. 6334-6345.

Research output: Contribution to journalArticle

Etogo, Anthony O. ; Nunez, Jesus ; Lin, Cheng Y. ; Toliver-Kinsky, Tracy ; Sherwood, Edward R. / NK but not CD1-restricted NKT cells facilitate systemic inflammation during polymicrobial intra-abdominal sepsis. In: Journal of Immunology. 2008 ; Vol. 180, No. 9. pp. 6334-6345.
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