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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

Generation of a Jurkat-based fluorescent reporter cell line to evaluate lipid antigen interaction with the human iNKT cell receptor

TL;DR: A novel iN KT reporter platform is created which facilitates the identification of antigenic structures that drive the activation of iNKT cells in health and disease and is characterized by a shorter turnaround time and lower costs.
Dissertation

Mécanismes cellulaires et moléculaires de l’immunodépression post-infectieuse

TL;DR: Ce travail introduit des perspectives nouvelles dans la physiopathologie de l’immunodepression post-infectieuse et suggere des applications therapeutiques potentielles.
Journal ArticleDOI

Inappropriate activation of invariant natural killer T cells and antigen‐presenting cells with the elevation of HMGB1 in preterm births without acute chorioamnionitis

TL;DR: Analysis of immune cells in the decidua of early to moderate PB without aCAM found that innate immunity and sterile inflammation are causes of PB in the absence of aC CAM.
Journal ArticleDOI

Harnessing the Versatility of Invariant NKT Cells in a Stepwise Approach to Sepsis Immunotherapy.

TL;DR: A double-hit treatment is designed that allows iNKT cells to escape anergy and exert beneficial effects in biphasic sepsis and may have translational potentials in the development of new therapies.
Journal ArticleDOI

Ether-linked lipids of Dermabacter hominis, a human skin actinobacterium.

TL;DR: The results demonstrate the existence of ether-linked lipids in D. hominis and reveal a differential distribution of phospholipids and glycolipids according to the sensitivity or resistance to daptomycin, although the mechanism(s) operating in the resistance to the antibiotic remain to be elucidated.
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.
Journal ArticleDOI

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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