CSDB: Search results

Sphingolipids, a lipid class characterized by a long-chain amino alcohol backbone, serve vital structural and signaling roles in eukaryotes. Though eukaryotes produce sphingolipids, this capacity is phylogenetically highly restricted in Bacteria. Intriguingly, bacterial species commonly associated in high abundance with eukaryotic hosts include sphingolipid producers, such as the Bacteroidetes in the mammalian gut. To date, a role for bacterial sphingolipids in immune system maturation has been described, but their fate and impact in host physiology and metabolism remain to be elucidated. The structural conservation of bacterial sphingolipids with those produced by their mammalian hosts offer clues about which aspects of mammalian biology may be modulated by these intriguing lipids.

metabolism, bacteria, physiology, immune responses, microbiome, sphingolipids

NCBI PubMed ID: 29328957
Publication DOI: 10.1016/j.mib.2017.12.011
Journal NLM ID: 9815056
Publisher: London; New York: Current Biology
Correspondence: rley@tuebingen.mpg.de
Institutions: Department of Microbiome Science, Max Planck Institute for Developmental Biology, Tubingen 72076, Germany, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14580, USA

T cells can recognize microbial antigens when presented by dedicated antigen-presenting molecules. While peptides are presented by classical members of the major histocompatibility complex (MHC) family (MHC I and II), lipids, glycolipids, and lipopeptides can be presented by the non-classical MHC member, CD1. The best studied subset of lipid-reactive T cells are type I natural killer T (iNKT) cells that recognize a variety of different antigens when presented by the non-classical MHCI homolog CD1d. iNKT cells have been shown to be important for the protection against various microbial pathogens, including B. burgdorferi, the causative agents of Lyme disease, and S. pneumoniae, which causes pneumococcal meningitis and community-acquired pneumonia. Both pathogens carry microbial glycolipids that can trigger the T cell antigen receptor (TCR), leading to iNKT cell activation. iNKT cells have an evolutionary conserved TCR alpha chain, yet retain the ability to recognize structurally diverse glycolipids. They do so using a conserved recognition mode, in which the TCR enforces a conserved binding orientation on CD1d. TCR binding is accompanied by structural changes within the TCR binding site of CD1d, as well as the glycolipid antigen itself. In addition to direct recognition of microbial antigens, iNKT cells can also be activated by a combination of cytokines (IL-12/IL-18) and TCR stimulation. Many microbes carry TLR antigens, and microbial infections can lead to TLR activation. The subsequent cytokine response in turn lower the threshold of TCR-mediated iNKT cell activation, especially when weak microbial or even self-antigens are presented during the cause of the infection. In summary, iNKT cells can be directly activated through TCR triggering of strong antigens, while cytokines produced by the innate immune response may be necessary for TCR triggering and iNKT cell activation in the presence of weak antigens. Here, we will review the molecular basis of iNKT cell recognition of glycolipids, with an emphasis on microbial glycolipids

glycolipids, CD1d, NKT cells, TCR, antigen-presentation, microbes

NCBI PubMed ID: 26300885
Publication DOI: 10.3389/fimmu.2015.00400
Journal NLM ID: 101560960
Publisher: Lausanne: Frontiers Research Foundation
Correspondence: dzajonc@liai.org
Institutions: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, USA

Recently, glycosphingolipids have been attracting attention due to their role on biological systems as second messengers or modulators of signal transduction, affecting several events, which range from apoptosis to regulation of the cell cycle. In pathogenic fungi, glycolipids are expressed in two classes: neutral monohexosylceramides (glucosyl-or galactosylceramide) and acidic glycosylinositol phosphorylceramides (the latter class carries longer glycan chains). It is worth to mention that monohexosylceramides exhibit significant structural differences in their lipid moieties compared to their mammalian counterparts, whereas the glycosylinositol phosphorylceramides exhibit remarkable structural differences in their carbohydrate moieties in comparison to mammal glycosphingolipids counterpart. We observed that glycosylinositol phosphorylceramides are capable of promoting immune response in infected humans. In addition, inhibiting fungal glycosphingolipid biosynthetic pathways leads to an inhibition of colony formation, spore germination, cell cycle, dimorphism and hyphal growth. Other pathogens, such as trypanosomatids, also present unique glycolipids, which may have an important role for the parasite development and/or disease establishment. Regarding host-pathogen interaction, cell membrane rafts, which are enriched in sphingolipids and sterols, participate in parasite/fungal infection. In this review, it is discussed the different biological roles of (glyco) (sphingo)lipids of pathogenic/opportunistic fungi and trypanosomatids.

glycosphingolipids, leishmania, glycosylinositol phosphorylceramides, inositol phosphorylceramide, membrane rafts, pathogenic fungi

NCBI PubMed ID: 19722017
Publication DOI: 10.1590/S0001-37652009000300012
Journal NLM ID: 7503280
Publisher: Academia Brasileira De Ciencias
Correspondence: straus.bioq@epm.br
Institutions: Setor de Imunoquímica de Glicoconjugados, Departamento de Bioquímica Ed. J.L. Prado, São Paulo, Brasil, Departamento de Microbiologia, Imunologia e Parasitologia, São Paulo, Brasil