Lipid antigens in immunity

Dowds, C. Marie; Kornell, Sabin-Christin; Blumberg, Richard S.; Zeißig, Sebastian

doi:10.1515/hsz-2013-0220

Cited by 37 publications

(32 citation statements)

References 210 publications

(397 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…First, we determined whether antigen recognition by T cells would up-regulate effector mediators reported to clear Chlamydia infections such as MHC-II [31], Cd1d2 [33], IFN-γ and Nos2 [34–36]. All mediators were up-regulated by vaccinated co-cultures in comparison to naïve co-cultures, irrespective of the stimuli (Fig.…”

Section: Resultsmentioning

confidence: 99%

Caveolin-mediated endocytosis of the Chlamydia M278 outer membrane peptide encapsulated in poly(lactic acid)-Poly(ethylene glycol) nanoparticles by mouse primary dendritic cells enhances specific immune effectors mediated by MHC class II and CD4+ T cells

et al. 2018

View full text Add to dashboard Cite

We previously developed a Chlamydia trachomatis nanovaccine (PPM) by encapsulating a chlamydial M278 peptide within poly(lactic acid)-poly(ethylene glycol) biodegradable nanoparticles that immunopotentiated Chlamydia-specific immune effector responses in mice. Herein, we investigated the mechanistic interactions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its uptake, trafficking, and T cell activation. Our results reveal that PPM triggered enhanced expression of effector cytokines and chemokines, surface activation markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2, Nod1), co-stimulatory (CD40, CD80, CD86) and MHC class I and II molecules. Co-culturing of PPM-primed DCs with T cells from C. muridarum vaccinated mice yielded an increase in Chlamydia-specific immune effector responses including CD3 lymphoproliferation, CD3CD4 IFN-γ-secreting cells along with CD3CD4 memory (CD44 and CD62L) and effector (CD44 and CD62L) phenotypes. Intracellular trafficking analyses revealed an intense expression and colocalization of PPM predominantly in endosomes. PPM also upregulated the transcriptional and protein expression of the endocytic mediator, caveolin-1 in DCs. More importantly, the specific inhibition of caveolin-1 led to decreased expression of PPM-induced cytokines and co-stimulatory molecules. Our investigation shows that PPM provided enhancement of uptake, probably by exploiting the caveolin-mediated endocytosis pathway, endosomal processing, and MHC II presentation to immunopotentiate Chlamydia-specific immune effector responses mediated by CD4 T cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Caveolin-mediated endocytosis of the Chlamydia M278 outer membrane peptide encapsulated in poly(lactic acid)-Poly(ethylene glycol) nanoparticles by mouse primary dendritic cells enhances specific immune effectors mediated by MHC class II and CD4+ T cells

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Further, neurotransmitter-dependent control of iNKT cells has recently been described [10]. Consistent with the wide variety of stimuli associated with the activation of iNKT cells and their potent effector functions, critical roles of iNKT cells have been described in various contexts ranging from antimicrobial immunity to the regulation of autoimmunity and cancer immunosurveillance [5,6,11]. …”

Section: Natural Killer T Cellsmentioning

confidence: 96%

“…Based on their T cell receptor (TCR) repertoire, NKT cells can be distinguished into invariant (i) or type I NKT cells and non-invariant or type II NKT cells [5]. iNKT cells express a semi-invariant TCR consisting of an invariant TCR-α chain (Vα14-Jα18 in mice and Vα24-Jα18 in humans), which pairs with a restricted set of TCR-β chains.…”

Section: Natural Killer T Cellsmentioning

confidence: 99%

“…iNKT cells express a semi-invariant TCR consisting of an invariant TCR-α chain (Vα14-Jα18 in mice and Vα24-Jα18 in humans), which pairs with a restricted set of TCR-β chains. iNKT cells recognize α-galactosylceramide (α-GalCer) in the context of CD1d and can be directly detected using α-GalCer-loaded CD1d tetramers [5]. Numerous studies have investigated the phenotype and function of iNKT cells and have demonstrated that these cells exhibit innate- or effector/memory-like functions characterized by immediate and robust cytokine secretion upon antigen recognition [6].…”

Section: Natural Killer T Cellsmentioning

confidence: 99%

“…NKT cells play critical roles in antimicrobial immunity, but can also contribute to inflammation and damage at mucosal surfaces [5,34,35]. Oxazolone colitis, a mouse model of the human inflammatory bowel disease (IBD) ulcerative colitis (UC), is characterized by superficial mucosal inflammation and epithelial destruction caused by iNKT cell-dependent secretion of IL-13 as well as IFN-γ [36–38].…”

Section: Regulation Of Mucosal Homeostasis Through Crosstalk Betwementioning

confidence: 99%

See 2 more Smart Citations

Control of intestinal homeostasis through crosstalk between natural killer T cells and the intestinal microbiota

Dowds

Blumberg

Zeißig

2015

Clinical Immunology

Self Cite

View full text Add to dashboard Cite

The human host and the intestinal microbiota co-exist in a mutually beneficial relationship, which contributes to host and microbial metabolism as well as maturation of the host’s immune system, among many other pathways (Tremaroli and Backhed, 2012; Hooper et al., 2012). At mucosal surfaces, and particularly in the intestine, the commensal microbiota provides ‘colonization resistance’ to invading pathogens and maintains homeostasis through microbial regulation of mucosal innate and adaptive immunity (Renz et al., 2012). Recent evidence suggests that natural killer T cells (NKT cells), a subgroup of lipid-reactive T cells, play central roles in bidirectional interactions between the host and the commensal microbiota, which govern intestinal homeostasis and prevent inflammation. Here, we provide a brief overview of recently identified pathways of commensal microbial regulation of NKT cells, discuss feedback mechanisms of NKT cell-dependent control of microbial colonization and composition, and highlight the critical role of host-microbial cross-talk for prevention of NKT cell-dependent mucosal inflammation.

show abstract

Glycolipid Presentation by CD1

Layre

Mazurek

Gilleron

2015

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

CD1 molecules constitute a family of nonpolymorphic, MHC class I‐like antigen‐presenting glycoproteins, which bind amphipathic lipid antigens and present them to T cells. These proteins are involved in presenting a broad range of self and foreign lipid antigens to variable T lymphocytes and natural killer T cells bearing a semi‐invariant T‐cell receptor ( iNKT ). It has become clear that the recognition of lipid antigens by T cells plays an important role in the detection and clearance of pathogens, immune response regulation and tissue surveillance. Key Concepts Self and microbial lipids and glycolipids are recognised by T cells. Hydrophobic pockets of CD1 proteins allow lipid antigens to be loaded via their alkyl chains, while the hydrophilic part of the antigen is presented to T‐cell receptors. CD1 proteins are non‐polymorphic and predominantly expressed on the surface of antigen‐presenting cells. Glycolipids can be processed into smaller antigenic structures in the endosomal pathway. CD1e, a soluble protein found in late endosomes, assists in lipid antigen editing and loading onto other CD1 proteins. CD1‐restricted T cells express αβ or γδ TCR and are found in CD4 + , CD8 + or double‐negative T‐cell populations. The frequency of autoreactive T cells is high among CD1‐restricted T cells.

show abstract

Lipid antigens in immunity

Cited by 37 publications

References 210 publications

Caveolin-mediated endocytosis of the Chlamydia M278 outer membrane peptide encapsulated in poly(lactic acid)-Poly(ethylene glycol) nanoparticles by mouse primary dendritic cells enhances specific immune effectors mediated by MHC class II and CD4+ T cells

Caveolin-mediated endocytosis of the Chlamydia M278 outer membrane peptide encapsulated in poly(lactic acid)-Poly(ethylene glycol) nanoparticles by mouse primary dendritic cells enhances specific immune effectors mediated by MHC class II and CD4+ T cells

Control of intestinal homeostasis through crosstalk between natural killer T cells and the intestinal microbiota

Glycolipid Presentation by CD1

Contact Info

Product

Resources

About