Interleukin-15 activates human natural killer cells to clear the intestinal protozoan Cryptosporidium

Sara M. Dann, Heuy Ching Wang, Kimberly J. Gambarin, Jeffrey K. Actor, Prema Robinson, Dorothy E. Lewis, Sophie Caillat-Zucman, A. Clinton White

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Intracellular protozoans of the genus Cryptosporidium are a major cause of diarrheal illness worldwide, but little is known about the mechanisms that control intestinal infection. We have previously demonstrated interleukin (IL)-15 expression in the intestinal mucosa of seronegative symptomatic volunteers after oral challenge with C. parvum, which suggests a role for IL-15 in the control of acute infection. We hypothesize that IL-15 activates an innate cytolytic cell response that contributes to the clearance of initial C. parvum infection. We report here that IL-15 activates peripheral blood mononuclear cells to lyse Cryptosporidium-infected epithelial cells in a dose-dependent manner. Lysis was due to CD3-CD16+CD56+ cells (i.e., natural killer [NK] cells). Furthermore, flow cytometry revealed that IL-15 increased expression of the activation receptor NKG2D on NK cells, particularly among the CD16Hi cytolytically active cells. Major histocompatibility complex class I-related molecules A and B (MICA and MICB), ligands for NKG2D, were increased after infection of epithelial cell lines and human ileal tissue. These data suggest that IL-15 has an important role in activating an NK cell-mediated pathway that leads to the elimination of intracellular protozoans from the intestines, which is a previously unrecognized feature of NK cell function.

Original languageEnglish (US)
Pages (from-to)1294-1302
Number of pages9
JournalJournal of Infectious Diseases
Volume192
Issue number7
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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