Interleukin-15 activates human natural killer cells to clear the intestinal protozoan cryptosporidium.
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.
Dann
Sara M
SM
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Wang
Heuy-Ching
HC
Gambarin
Kimberly J
KJ
Actor
Jeffrey K
JK
Robinson
Prema
P
Lewis
Dorothy E
DE
Caillat-Zucman
Sophie
S
White
A Clinton
AC
D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D003457:Cryptosporidiosis / Q000276:immunology / Q000469:parasitology; D016785:Cryptosporidium parvum / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000276:immunology / Q000469:parasitology; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000469:parasitology; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology* / Q000469:parasitology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell
D019409:Interleukin-15; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell