TY - JOUR
T1 - 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.
AU - Tanaka, Sachi
AU - Koizumi, Shin Ichi
AU - Masuko, Kazutaka
AU - Makiuchi, Naoko
AU - Aoyagi, Yuka
AU - Quivy, Emi
AU - Mitamura, Rieko
AU - Kano, Tsutomu
AU - Ohkuri, Takayuki
AU - Wakita, Daiko
AU - Chamoto, Kenji
AU - Kitamura, Hidemitsu
AU - Nishimura, Takashi
N1 - Funding Information:
We thank Dr. Shizuo Akira (Osaka University) for the kind donation of TLR2 −/− , TLR4 −/− , and TLR9 −/− mice. This work was partially supported by Grant-in-Aid for a National Project “Knowledge Cluster Initiative” (2nd stage, “Sapporo Biocluster Bio-S”) from Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) , Grant-in Aid for Scientific Research (B), Grant-in Aid for Young Scientists (B) and JSPS Research Fellowship for Young Scientists ( 21-2717 to ST and 22-5171 to SK).
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.intimp.2010.11.026
DO - 10.1016/j.intimp.2010.11.026
M3 - Article
C2 - 21144920
AN - SCOPUS:79151475544
VL - 11
SP - 226
EP - 232
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 2
ER -