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

Sara Dann-Grice, 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 Citations (Scopus)

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

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Interleukin-15
Cryptosporidium
Natural Killer Cells
Infection Control
NK Cell Lectin-Like Receptor Subfamily K
Epithelial Cells
Intestinal Mucosa
Infection
Major Histocompatibility Complex
Intestines
human IL15 protein
Volunteers
Blood Cells
Flow Cytometry
Ligands
Cell Line

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Interleukin-15 activates human natural killer cells to clear the intestinal protozoan Cryptosporidium. / Dann-Grice, Sara; Wang, Heuy Ching; Gambarin, Kimberly J.; Actor, Jeffrey K.; Robinson, Prema; Lewis, Dorothy E.; Caillat-Zucman, Sophie; White, A. Clinton.

In: Journal of Infectious Diseases, Vol. 192, No. 7, 01.09.2005, p. 1294-1302.

Research output: Contribution to journalArticle

Dann-Grice, Sara ; Wang, Heuy Ching ; Gambarin, Kimberly J. ; Actor, Jeffrey K. ; Robinson, Prema ; Lewis, Dorothy E. ; Caillat-Zucman, Sophie ; White, A. Clinton. / Interleukin-15 activates human natural killer cells to clear the intestinal protozoan Cryptosporidium. In: Journal of Infectious Diseases. 2005 ; Vol. 192, No. 7. pp. 1294-1302.
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