Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria

被引:266
作者
Kinjo, Yuki [1 ,2 ]
Illarionov, Petr [3 ]
Vela, Jose Luis [1 ]
Pei, Bo [1 ]
Girardi, Enrico [4 ]
Li, Xiangming [5 ]
Li, Yali [4 ]
Imamura, Masakazu [6 ,7 ]
Kaneko, Yukihiro [2 ]
Okawara, Akiko [2 ]
Miyazaki, Yoshitsugu [2 ]
Gomez-Velasco, Anaximandro [8 ]
Rogers, Paul [9 ]
Dahesh, Samira [10 ,11 ]
Uchiyama, Satoshi [10 ,11 ]
Khurana, Archana [1 ]
Kawahara, Kazuyoshi [12 ]
Yesilkaya, Hasan [13 ]
Andrew, Peter W. [13 ]
Wong, Chi-Huey [6 ,7 ]
Kawakami, Kazuyoshi [14 ]
Nizet, Victor [10 ,11 ]
Besra, Gurdyal S. [3 ]
Tsuji, Moriya [5 ]
Zajonc, Dirk M. [4 ]
Kronenberg, Mitchell [1 ]
机构
[1] La Jolla Inst Allergy & Immunol, Div Dev Immunol, La Jolla, CA USA
[2] Natl Inst Infect Dis, Dept Chemotherapy & Mycoses, Tokyo, Japan
[3] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England
[4] La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA USA
[5] Rockefeller Univ, HIV & Malaria Vaccine Program, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA
[6] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
[7] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[8] Univ British Columbia, Dept Med, Div Infect Dis, Vancouver, BC, Canada
[9] Kyowa Hakko Kirin Calif Inc, La Jolla, CA USA
[10] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA
[11] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA
[12] Kanto Gakuin Univ, Dept Appl Mat & Life Sci, Coll Engn, Yokohama, Kanagawa, Japan
[13] Univ Leicester, Dept Infect Immun & Inflammat, Leicester, Leics, England
[14] Tohoku Univ, Dept Med Microbiol Mycol & Immunol, Grad Sch Med, Sendai, Miyagi 980, Japan
基金
英国惠康基金; 美国国家卫生研究院; 日本学术振兴会;
关键词
NKT CELLS; STREPTOCOCCUS-PNEUMONIAE; ANTIGENS; INNATE; ACTIVATION; CD1D; IDENTIFICATION; INFECTION; DISEASE; BURDEN;
D O I
10.1038/ni.2096
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Natural killer T cells (NKT cells) recognize glycolipid antigens presented by CD1d. These cells express an evolutionarily conserved, invariant T cell antigen receptor (TCR), but the forces that drive TCR conservation have remained uncertain. Here we show that NKT cells recognized diacylglycerol-containing glycolipids from Streptococcus pneumoniae, the leading cause of community-acquired pneumonia, and group B Streptococcus, which causes neonatal sepsis and meningitis. Furthermore, CD1d-dependent responses by NKT cells were required for activation and host protection. The glycolipid response was dependent on vaccenic acid, which is present in low concentrations in mammalian cells. Our results show how microbial lipids position the sugar for recognition by the invariant TCR and, most notably, extend the range of microbes recognized by this conserved TCR to several clinically important bacteria.
引用
收藏
页码:966 / U72
页数:10
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