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

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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.

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Journal ArticleDOI

Tissue-Resident Lymphocytes Across Innate and Adaptive Lineages.

TL;DR: An overview of the heterogeneous tissue-resident lymphocyte populations is provided, their development is discussed, and their functions both in the context of microbial infection and cancer are highlighted.
Journal ArticleDOI

Turned on by danger: activation of CD1d-restricted invariant natural killer T cells.

Victoria Lawson
- 01 Sep 2012 - 
TL;DR: This work has characterized precisely how iNKT cells are activated by exogenous antigen, or by a combination of dendritic cell‐derived interleukin‐12 andiNKT TCR–self‐antigen–CD1d engagement, and is informing the design of synthetic iN KT‐cell antigens.
Journal ArticleDOI

Structure-activity relationship studies of novel glycosphingolipids that stimulate natural killer T-cells.

TL;DR: A large number of analogs of KRN7000 show potent bioactivities and have the potential of being utilized as therapeutic agents, and structure-activity relationship studies of novel glycolipids which stimulate NKT cells efficiently are summarized.
Journal ArticleDOI

The processing and presentation of lipids and glycolipids to the immune system

TL;DR: The overall sequence of events needed for efficient presentation of lipid antigens is now understood and presented and new approaches to address them are described during the characterization of lipids and glycolipids antigen presentation.
Journal ArticleDOI

Development and function of murine RORγt+ iNKT cells are under TGF-β signaling control.

TL;DR: This work demonstrates that both the development and responsiveness of the newly described IL-17-producing iNKT cell subset is under the control of a dedicated TGF-β signaling pathway.
References
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Journal Article

Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC.

TL;DR: Although universal screening for GBS colonization is anticipated to result in further reductions in the burden of GBS disease, the need to monitor for potential adverse consequences of intrapartum antibiotic use, such as emergence of bacterial antimicrobial resistance or increased incidence or severity of non-GBS neonatal pathogens, continues.
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Innate Immunity: The Virtues of a Nonclonal System of Recognition

TL;DR: Characterization of the nonclonal receptors of the innate immune system responsible for the adjuvant activity, and, evidently, for the associated side effects, would provide a powerful alternative approach, which would ultimately allow one to target these receptors directly.
Journal ArticleDOI

CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides.

TL;DR: Glycosylceramide-mediated proliferative responses of Valpha14 NKT cells were abrogated by treatment with chloroquine-concanamycin A or by monoclonal antibodies against CD1d/Vbeta8, CD40/CD40L, or B7/CTLA-4/CD28, but not by interference with the function of a transporter-associated protein.
Journal ArticleDOI

The global burden of group A streptococcal diseases

TL;DR: The need to reinforce current control strategies, develop new primary prevention strategies, and collect better data from developing countries for most diseases is highlighted, as GAS is an important cause of morbidity and mortality.
Journal ArticleDOI

Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates

TL;DR: The burden of pneumococcal pneumonia is measured by applying the proportion of pneumonia cases caused by S pneumoniae derived from efficacy estimates from vaccine trials to WHO country-specific estimates of all-cause pneumonia cases and deaths, using disease incidence and case-fatality data from a systematic literature review.
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