Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria
Yuki Kinjo,Petr A. Illarionov,Jose Luis Vela,Bo Pei,Enrico Girardi,Xiangming Li,Yali Li,Masakazu Imamura,Yukihiro Kaneko,Akiko Okawara,Yoshitsugu Miyazaki,Anaximandro Gómez-Velasco,Paul R. Rogers,Samira Dahesh,Satoshi Uchiyama,Archana Khurana,Kazuyoshi Kawahara,Hasan Yesilkaya,Peter W. Andrew,Chi-Huey Wong,Kazuyoshi Kawakami,Victor Nizet,Gurdyal S. Besra,Moriya Tsuji,Dirk M. Zajonc,Mitchell Kronenberg +25 more
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TLDR
The results show how microbial lipids position the sugar for recognition by the invariant TCR and extend the range of microbes recognized by this conserved TCR to several clinically important bacteria.Abstract:
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.read more
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C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia.
Friederike Behler-Janbeck,Tomotsugu Takano,Regina Maus,Jennifer Stolper,Danny Jonigk,Meritxell Tort Tarrés,Thomas Fuehner,Antje Prasse,Tobias Welte,Mattie S. M. Timmer,Bridget L. Stocker,Yoichi Nakanishi,Tomofumi Miyamoto,Sho Yamasaki,Ulrich A. Maus +14 more
TL;DR: The Mincle-Glc-DAG axis is a hitherto unrecognized element of lung protective immunity against focal pneumonia induced by S. pneumoniae.
Journal ArticleDOI
Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection.
Yan Wang,Bin Jiang,Yongli Guo,Wenchao Li,Ying Tian,Gregory F. Sonnenberg,Jeffery N. Weiser,Jeffery N. Weiser,Xin Ni,Hao Shen,Hao Shen +10 more
TL;DR: Results indicate that memory Th17 cells had a key role in providing protection against pneumonia in a serotype-independent manner and suggest the feasibility of developing a broadly protective vaccine against bacterial pneumonia by targeting mucosal Th17 T cells.
Journal ArticleDOI
The Role of Invariant Natural Killer T Cells in Dendritic Cell Licensing, Cross-Priming, and Memory CD8+ T Cell Generation
TL;DR: The role of iNKT cells is focused on in the cross-talk with cross-priming DC and memory CD8+ T cell formation, which enhances immune responses against bacterial pathogens or parasites but also play a role in viral infections.
Journal ArticleDOI
Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion Injury
Jianjun Zhang,Conghui Han,Hui-Juan Dai,Jianquan Hou,Yang Dong,Xiao-Lan Cui,Longmei Xu,Ming Zhang,Qiang Xia +8 more
TL;DR: A hypoxia/HIF-2α/adenosine A2A receptor axis that restricts NKT cell activation when confronted with oxidative stress and thus protects against renal IRI is revealed.
Journal ArticleDOI
The Mechanism of Splenic Invariant NKT Cell Activation Dictates Localization In Vivo
Irah L. King,Eyal Amiel,Mike Tighe,Katja Mohrs,Natacha Veerapen,Gurdyal S. Besra,Markus Mohrs,Elizabeth A. Leadbetter +7 more
TL;DR: It is found that iNKT cells consolidate in the marginal zone and require dendritic cells lining the splenic marginal zone for activation following administration of cognate glycolipids and during systemic infection but not following exogenous cytokine administration.
References
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