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2016.12.03
Kazuyoshi TakedaDivision of Cell Biology, Biomedical Research Center
and Department of Biofunctional Micribiota, Graduate School of Medicine,
Juntendo University, Tokyo, Japan
8th INDIA PROBIOTIC SYMPOSIUM“PROBITOTICS IN HEALTH-EMERGING OPPORTUNITIES”
Enhancement of Natural Killer Cell Activityby Probiotics
Session 1: Probiotics in Allergy and Immunity
= reactions to eliminate foreign material (non-self) from the body (self) by lymphoid cells
→ rejection in organ transplantation
virus, bacteria, parasites
cancer cells = crazy non-stop growing cells out of controlThe crazy marks are expressed on cell surface.
Immune cells attack cancer cellsbasing on the recognition of these crazy marks.
Immunity = mechanisms to avoid diseases
Not distinguish an enemy from a friend
How about cancer cell? Cancer cells are originally derived from a self cell
≒ pathogens
rough recognition strictly recognize one cell responses to many ( handy man )
one cell response to one (specialist )
How much does it cost for activation?
Improved by habits and/or diet Activated by vaccination
instable(sensitive to many stimulants)
stable
so so
cheep
quick
skillful
high
slownot at the first encounterlearn and rememberquick response at the 2nd encounter
at the first encounterquick response
Natural Immue Res. Acquired Immune Res.
Immunity
Speed of start up
Recognition of enemy
= Natural immunity+ Acquired immunity
when memory is kept,never get same disease
resistant to diseases,but not completely
not completely prevent/cure completely prevent/cure
eat help kill makeantibodies
NK cellMacrophage B cell
4 8
T cell
kill
Front line Headquarters
Front line provides the information of the enemy.
At the second invasion of same enemy, headquarters promptly attack with more effective ways based on the information provided by front line at first encounter.
1 : natural immunity 2 : acquired immunityquick, cheap, and so so slow, expensive, and skillful
HELP
information
natural immunity acquired immunity
4 8
4 8
4 8
foreign bodiesforeign bodies
attack
attac
k
attack
attack
attac
k
attack
foreign bodies
attack
attack
attack
information
Dendritic cells(DC)
information
dendritic cells (DC)
HELP
information
natural immunity acquire immunity
4 8
4 8
4 8att
ack
attackatt
ack
foreignbodyforeignbodyforeignbody
prompt and forceful attackby activated CD8T and B cells
attac
k
information
dendritic cells (DC)
prompt and forceful attackby activated CD8T and B cells attack
information
dendritic cells (DC)
Cooperation of two kinds of immunity in self-defense
Bacteria Virus Tumor cells
NK cell: natural killer cell : born killer cell one subset of lymphocytes killing the
cells that do not belong to self even at the first encounter
What is NK cell ?
NK cell activity (killing activity) = how many tumor cells NK cells can kill in 4 h (%)
100806040200NK cell activity (%)
Num
ber o
f per
sons
NK cell activity (killing activity) is various individually.
The patients genetically impaired in NK cell, but not T and B cells, suffer from severe infections with herpes virus.
What does happen in the human who has no NK cells or low NK cell activity ?
Elderly humans with low NK cell activity exhibit a higher mortality rate due to infectious diseases compared with their counterparts with high NK cell activity.
Epidemiological study revealed that the population with low NK cell activity has a significantly higher risk of cancer than the population with intermediate or high NK cell activity.
Decrease in NK cell number and/or activity
↓Higher risk of cancer development and
infectious diseases
↓Augmentation of NK cell activity
possibly reduces the risk of cancer development and infectious diseases
↓How augment NK cell activity in daily life?
Supplementation of live beneficial bacteriapromotes health and reduces the risk of various diseases.
Probiotics are live microorganisms which,when administered in adequate amounts,confer a health benefit on the host. (FAO/WHO 2001)
yoghurt, fermented foods, some mushrooms, etc
Improvement of the dietary habitstake good foods for health and reduce ill foods
Yakult : Fermented milk drink containing Live Lactobacillus casei Shirota (LcS)
Do probiotics augment NK cell activity?
Augmentation of NK cell activity by LcS intake
%
%
(E/T =20)
LcS more effectively augments NK cell activity in the people who need NK cell activation.
NK cell activation by LcS is more effectivein the persons who have lower NK cell activity
To activate NK cells by the oral intake of LcS,LcS must go into the body through epithelium.
Such experiments do not sufficiently explainhow LcS augment NK cell activity in vivo.
M. Takahashi, et al.
LcS
Lactic acid bacteria phagocytized by M cells
LcS
M cell
Intestine
NK cell
Macrophageand/or
Dendriticcell
T cell
CBLcSCB
Enteric microbiota Commensal bacteria
Regulation
Mucosal ImmunityIntestinal Immunity
LcS
LcS enter into the body through M cell at intestine
Correlation between augmentation of cytotoxic activityand IL-12 production in LcS-induced NK cell activation
PBMC were co-cultured with freeze-dried LcS in vitro
M cell
Intestine
CancerPathogens
LcS LcS
IL-12activation
activation by contact
IFN-g
NK cell
Macrophageand/or
Dendriticcell
Possible mechanisms of LcS-induced NK cell activation
activation
Probiotics augments NK cell activity via the enhancement of immune responses in intestine
1. Probiotics possibly enter into a body at intestine.
2. DC and Mf recognize probiotics and produce NK cell activating cytokines (e.g. IL-12, IFN-g).3. NK cells are activated and would prevent diseases.
4 8
4 8
4 8
LcS
LcS
LcS
LcS
LcS
LcS
LcS
LcS
LcS
Juntendo University, School of MedicineDepartment of Immunology
K. OkumuraF. Nagao
Yalult Central Institute for Microbiological ResearchM. NannoT. SuzukiK. ShidaS. -I. ShimadaY. MatsuokaY. Yamaoka
Takane HospitalH. Takane
Acknowledgements