IL-18, but not IL-15, contributes to the IL-12-dependent induction of NK-cell effector functions by Leishmania infantum in vivo.
Activation of NK cells is a hallmark of infections with intracellular pathogens. We previously showed that the protozoan parasite Leishmania infantum triggered a rapid NK-cell response in mice that required TLR9-positive myeloid DC and IL-12, but no IFN-alpha/beta. Here, we investigated whether IL-15 or IL-18 mediate the activity of IL-12 or function as independent activators of NK cells. In contrast to earlier studies that described IL-15 as crucial for NK-cell priming in response to TLR ligands, the expression of IFN-gamma, FasL, perforin and granzyme B by NK cells in L. infantum-infected mice was completely preserved in the absence of IL-15, whereas the proliferative capacity of NK cells was lower than in WT mice. IFN-gamma secretion, cytotoxicity and FasL expression of NK cells from infected IL-18(-/-) mice were significantly reduced compared with controls, but, unlike IL-12, IL-18 was not essential for NK-cell effector functions. Part of the NK-cell-stimulatory effect of IL-12 was dependent on IL-18. We conclude that IL-15 is not functioning as a universal NK-cell priming signal and that IL-18 contributes to the NK-cell response in visceral leishmaniasis. The cytokine requirements for NK-cell activation appear to differ contingent upon the infectious pathogen.
Haeberlein
Simone
S
Microbiology Institute - Clinical Microbiology, Immunology and Hygiene, Friedrich-Alexander-University Erlangen-Nuremberg and University Clinic of Erlangen, Erlangen, Germany.
Sebald
Heidi
H
Bogdan
Christian
C
Schleicher
Ulrike
U
D000818:Animals; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D018314:Leishmania infantum / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis
D019409:Interleukin-15; D020382:Interleukin-18; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma