TY - JOUR
T1 - Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria
AU - Kinjo, Yuki
AU - Illarionov, Petr
AU - Vela, José Luis
AU - Pei, Bo
AU - Girardi, Enrico
AU - Li, Xiangming
AU - Li, Yali
AU - Imamura, Masakazu
AU - Kaneko, Yukihiro
AU - Okawara, Akiko
AU - Miyazaki, Yoshitsugu
AU - Gómez-Velasco, Anaximandro
AU - Rogers, Paul
AU - Dahesh, Samira
AU - Uchiyama, Satoshi
AU - Khurana, Archana
AU - Kawahara, Kazuyoshi
AU - Yesilkaya, Hasan
AU - Andrew, Peter W.
AU - Wong, Chi Huey
AU - Kawakami, Kazuyoshi
AU - Nizet, Victor
AU - Besra, Gurdyal S.
AU - Tsuji, Moriya
AU - Zajonc, Dirk M.
AU - Kronenberg, Mitchell
N1 - Funding Information:
We thank S. Akira (Osaka University) for Myd88−/− mice; B. Beutler (Scripps Research Institute) for Myd88−/−TrifLps2/Lps2 mice; M. Antony (University of Birmingham) for group B Streptococcus A909; N. Yamamoto, T. Kinjo, G.D. Ainge, D. Gibson and G. Painter for suggestions; N. Sato for help with glycolipid analysis; and C. Lena for technical assistance. Supported by the US National Institutes of Health (AI45053 and AI71922 to M.K., AI074952 to D.M.Z.; AI070258 to M.T.; and F32AI083029 to J.L.V.), the Japan Society for the Promotion of Science and Ministry of Education, Culture, Sports, Science and Technology (22689031), the Ministry of Health, Labor and Welfare of Japan (H22seisakusouyakuippan012), the Uehara Memorial Foundation (Y.Ki.), the Wellcome Trust, the Royal Society, J. Bardrick (G.S.B.) and the Cancer Research Institute (D.M.Z.).
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
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U2 - 10.1038/ni.2096
DO - 10.1038/ni.2096
M3 - Article
C2 - 21892173
AN - SCOPUS:80052966551
SN - 1529-2908
VL - 12
SP - 966
EP - 974
JO - Nature Immunology
JF - Nature Immunology
IS - 10
ER -