Heat-killed Lactobacillus acidophilus La205 enhances NK cell cytotoxicity through increased granule exocytosis.
Heat-killed lactic acid bacteria (LAB) are known to be important immunomodulators that stimulate tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production as well as increase phagocytic activity in macrophages. NK cells play a critical role in innate immune response and induce spontaneous killing of tumor cells and virus-infected cells. However, the effect of heat-killed LAB on NK cells is still unclear. In this study, we investigated the effect of heat-killed Lactobacillus acidophilus La205 (La205) on NK cytolytic activity. We found that heat-killed La205 directly stimulated NK cytolytic activity in dose- and time-dependent manners. To determine the mechanism underlying heat-killed La205-enhanced NK cytotoxicity, the expression of NK activating receptors was tested. Heat-killed La205 did not affect the expression of NK activating receptors. To investigate whether NK degranulation is related to heat-killed La205-enhanced NK cytotoxicity, NK degranulation inhibitor concanamycin A (CMA) was used. CMA effectively blocked heat-killed La205-induced NK cytotoxicity, and an assay for detection of a degranulation marker, CD107a, showed that heat-killed La205 increased granule exocytosis approximately 2-fold in comparison to non-treated NK cells. In addition, heat-killed La205 dramatically elevated mRNA expression of granulysin, a component of the cytolytic granule contents, in NK cells. However, other granule contents, including perforin and granzymes, were not changed by heat-killed La205. From these data, we concluded that heat-killed La205 stimulated NK cytolytic activity through enhancement of granule exocytosis, and granulysin may be a critical mediator in heat-killed La205-induced granule exocytosis.
Department of Life Science, Sookmyung Women's University, Seoul, Republic of Korea.
Soyoung
S
Cheon
Ki Woong
KW
Lee
Kyung Eun
KE
Kim
Jung Kyu
JK
Park
Sunyoung
S
Park
Chul-hyun
CH
Kim
Daejin
D
Kim
Hyong Joo
HJ
Lee
Daeho
D
Cho
D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D003594:Cytoplasmic Granules / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005089:Exocytosis / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D007779:Lactobacillus acidophilus / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human; D053804:Granzymes