Attenuated Listeria infection activates natural killer cell cytotoxicity to regress melanoma growth in vivo.
Listeria monocytogenes infection induces various types of immune responses. The Lm-induced immunity not only protects the hosts against Lm infection but also has a therapeutic effect on other diseases such as tumors and infectious diseases. In the present study, we sought to identify the cells and molecules that are primarily responsible for the Lm-induced antitumor immune response. We investigated the mechanism of the antitumor immune response induced by Lm infection using melanoma cells and various types of gene-manipulated mice and B16F10 melanoma cells. Melanoma cells were implanted into mice intrasplenically or intraperitoneally. Lm infection of mice remarkably suppressed the growth of transplanted melanoma. The suppression of melanoma growth was due to the augmented NK cytotoxicity. The Lm-induced NK activation against melanoma was type I interferon- and signal transducer and activator of transcription (STAT)1-dependent but independent of IL-12 and IFN-gamma. In contrast to avirulent Listeria innocua and hly(-) Lm failed to induce NK activation, a mutant Lm strain with minimal hemolytic activity and with normal accessibility to cytoplasm-induced NK activation. We demonstrated that the attenuated Lm entrance into the cytoplasm induces the production of type I IFN followed by the activation of NK cells, which is essential for the Lm-induced antitumor response.
Shen
Hua
H
Department of Immunology and Host Defenses, Ehime University Graduate School of Medicine, Ehime, Japan.
Kanoh
Makoto
M
Maruyama
Saho
S
Matsumoto
Akira
A
Zhang
Wei
W
Asano
Yoshihiro
Y
D000818:Animals; D007370:Interferon Type I / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor / Q000276:immunology; D013154:Spleen / Q000473:pathology; D016019:Survival Analysis
D007370:Interferon Type I; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D018664:Interleukin-12; D007371:Interferon-gamma