Human congenital infection with Trypanosoma cruzi induces phenotypic and functional modifications of cord blood NK cells.
We studied the phenotype and activity of cord blood natural killer (NK) cells in newborns congenitally infected with Trypanosoma cruzi. We found that the proportion of CD56(bright) NK cells was significantly decreased in cord blood from these newborns, suggesting they may have been recruited to secondary lymphoid organs. The remaining CD56(bright) NK cells exhibited a defective ability in the production of interferon (IFN)-gamma following in vitro activation with interleukin (IL)-12 + IL-2 or IL-12 + IL-15 cytokines, as compared with NK cells from uninfected newborns. In addition, cord blood NK cells from congenitally infected newborns stimulated with cytokines have a decreased release of granzyme B (GrB) when incubated with K562 target cells. This defect in cytotoxic effector function is associated with a reduced surface expression of activating NK receptors (NKp30, NKp46, and NKG2D) on CD56(dim) NK cells compared with uninfected newborns. These alterations of fetal NK cells from congenitally infected newborns may reflect a down-regulation of the NK cell response after an initial peak of activation and could also be the result of T. cruzi modulating the immune response.
Hermann
Emmanuel
E
Laboratoire de Parasitologie, Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium.
Alonso-Vega
Cristina
C
Berthe
Aurelie
A
Truyens
Carine
C
Flores
Amilcar
A
Cordova
Marisol
M
Moretta
Lorenzo
L
Torrico
Faustino
F
Braud
Veronique
V
Carlier
Yves
Y
D000818:Animals; D019002:CD56 Antigen / Q000032:analysis; D014355:Chagas Disease / Q000151:congenital* / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation; D005312:Fetal Blood / Q000166:cytology / Q000469:parasitology*; D053804:Granzymes; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D010641:Phenotype; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D012697:Serine Endopeptidases / Q000378:metabolism; D014349:Trypanosoma cruzi
D019002:CD56 Antigen; D019409:Interleukin-15; D007376:Interleukin-2; C527085:KLRK1 protein, human; D008562:Membrane Glycoproteins; C112260:NCR1 protein, human; C431710:NCR3 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D018664:Interleukin-12; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases