title: Toll-like receptor-dependent IL-12 production by dendritic cells is required for activation of natural killer cell-mediated Type-1 immunity induced by Chrysanthemum coronarium L.
abstract: Type-1 immunity has an essential role for our host defenses against cancer and outer pathogens such as bacteria and virus. We demonstrated here that the edible plant extract of Chrysanthemum coronarium L. (C. coronarium) remarkably activates Type-1 immunity in a Toll-like receptor (TLR)2-, TLR4-, and TLR9-dependent manner. In the present experiments, the extract of C. coronarium significantly induces interferon (IFN)-γ production by mouse spleen cells. In addition, the IFN-γ production by spleen cells was completely blocked by the addition of anti-Interleukin (IL)-12 monoclonal antibodies. We confirmed that NK1.1(+) natural killer (NK) cells, NKT cells, and CD11c(+) dendritic cells (DC) were immediately activated after the stimulation with the extract of C. coronarium and the IFN-γ production was abolished in NK1.1(+) cell-depleted spleen cells. The stimulation with the extract of C. coronarium caused DC maturation involving with up-regulations of surface expression levels of MHC class I, MHC class II, CD40, and CD86 as well as induction of IL-12 production. The IFN-γ production induced by the extract was significantly reduced in the spleen cells depleted CD11c(+) cells. Furthermore, the IFN-γ production after the stimulation was strongly reduced in TLR4- and partially in TLR2- and TLR9-deficient spleen cells. Thus, we demonstrated the cellular mechanism for the activation of Type-1 immunity via NK cells, NKT cells, and DC by the extract of C. coronarium. These findings strongly suggest that C. coronarium would be a promising immuno-improving adjuvant, which might be useful for prevention of infectious, cancer, and allergic diseases through the activation of Type-1 immunity.
authors.affiliation: Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Sachi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Koizumi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Masuko
authors.forename: Naoko
authors.initials: N
authors.lastname: Makiuchi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Emi
authors.initials: E
authors.lastname: Quivy
authors.forename: Rieko
authors.initials: R
authors.lastname: Mitamura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kano
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohkuri
authors.forename: Daiko
authors.initials: D
authors.lastname: Wakita
authors.forename: Kenji
authors.initials: K
authors.lastname: Chamoto
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Kitamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D031202:Chrysanthemum / Q000737:chemistry*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D010945:Plants, Edible / Q000737:chemistry; D013154:Spleen / Q000166:cytology / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000502:physiology*
chemical_list: D010936:Plant Extracts; D051193:Toll-Like Receptors; D018664:Interleukin-12; D007371:Interferon-gamma