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NK Cells Eliminate Cryptococcus neoformans by Potentiating the Fungicidal Activity of Macrophages Rather than by Directly Killing Them upon Stimulation with IL‐12 and IL‐18
Author(s) -
Kawakami Kazuyoshi,
Koguchi Yoshinobu,
Qureshi Mahboob Hossain,
Yara Satomi,
Kinjo Yuki,
Uezu Koari,
Saito Atsushi
Publication year - 2000
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2000.tb02601.x
Subject(s) - cryptococcus neoformans , biology , interleukin 12 , microbiology and biotechnology , stimulation , macrophage , cytotoxic t cell , cell culture , cytokine , interleukin 21 , immune system , immunology , t cell , in vitro , biochemistry , genetics , neuroscience
In the present study, we examined whether natural killer (NK) cells have direct fungicidal activity against Cryptococcus neoformans . Splenic NK cells were obtained from SCID mice and stimulated with a combination of interleukin (IL)‐12 and IL‐18 in flat culture plates or round tubes. They were then or at the same time cultured with the yeast cells and the number of viable yeast cells was examined. We could not detect direct fungicidal activity by NK cells under any culture condition, although they produced a large amount of IFN‐γ and exerted marked cytotoxic activity against YAC‐1 cells. On the other hand, NK cells significantly potentiated the nitric oxide‐mediated cryptococcocidal activity of thioglycolate‐elicited peritoneal macrophages obtained from SCID mice upon stimulation with IL‐12 and IL‐18. The culture supernatants of NK cells stimulated with IL‐12 and IL‐18 provided similar results when used in place of NK cells. The induction of macrophage anticryptococcal activity by NK cells and NK cell culture supernatants were both mediated by IFN‐γ because the specific mAb almost completely abrogated such effect. Considered collectively, our results suggested that NK cells may play a regulatory role in potentiating macrophage‐mediated fungicidal mechanisms in host resistance to infection with C. neoformans rather than exerting a direct killing activity against the fungal pathogen.