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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

Stages versus subsets: Invariant Natural Killer T cell lineage differentiation.

TL;DR: The molecules regulating the differentiation of iNKT cell lineages, the transcription factors associated with their development, and the role of E protein transcription factors and their negative regulators the Id proteins are discussed, as these cells develop from immature progenitor cells to terminally differentiated cells in peripheral tissue.

glycolipid through IFNγ produced in part by iNKT cells

TL;DR: The results indicate that coinfecting commensal bacteria exacerbate C. albicans infection through IFN-γ produced, in part, by iNKT cells, which is a major cause of invasive fungal infections.
Journal ArticleDOI

The role of invariant NKT cells in organ-specific autoimmunity.

Di Pietro C, +1 more
TL;DR: The possible mechanism of action and final effect of the different iNKT cell subsets in the pathogenesis of T cell-mediated autoimmune diseases are reviewed and the role of NKT17 cells is raised.
Journal ArticleDOI

Activation of invariant natural killer T cells stimulated with microbial α-mannosyl glycolipids

TL;DR: These results suggest that these microbial α-mannosyl glycolipids are capable of being recognized by both the invariant TCR and PRRs and inducing immune responses.
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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