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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

Recognition of Microbial Glycolipids by Natural Killer T Cells

TL;DR: iNKT cells can be directly activated through TCR triggering of strong antigens, while cytokines produced by the innate immune response may be necessary for TCRTriggering and iNKT cell activation in the presence of weak antIGens.
Journal ArticleDOI

Activation strategies for invariant natural killer T cells.

TL;DR: Both lipid antigens and PAMPs mediate reciprocal activation of iNKT cells and APCs, leading to downstream activation of multiple other immune cell types to promote pathogen clearance.
Journal ArticleDOI

The functions of type I and type II natural killer T cells in inflammatory bowel diseases.

TL;DR: The present knowledge on the antigen recognition, activation, and function of NKT cells is summarized with a particular focus on their role in inflammatory bowel disease and factors that may influence the functional outcome of N KT cell responses in intestinal inflammation are discussed.
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Mechanisms of Bacterial Superinfection Post-influenza: A Role for Unconventional T Cells.

TL;DR: The main features of influenza viruses and current knowledge about the mechanical and immune mechanisms that underlie post-influenza secondary bacterial infections are reviewed and two major opportunistic pathogens involved in superinfections are focused on, namely Streptococcus pneumoniae and Staphylococcus aureus.
Journal ArticleDOI

Influenza A virus-induced release of interleukin-10 inhibits the anti-microbial activities of invariant natural killer T cells during invasive pneumococcal superinfection

TL;DR: Overall, iNKT cells have a beneficial role (upstream of bacterial colonization) in controlling influenza-pneumococcal superinfection, although they represent novel targets of immunosuppression at the time of bacterial challenge.
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.
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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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