Mannose Binding

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The glycosylation pattern of common allergens: the recognition and uptake of Der p 1 by epithelial and dendritic cells is carbohydrate dependent.

Allergens are initiators of both innate and adaptive immune responses. They are recognised at the site of entry by epithelial
and dendritic cells (DCs), both of which activate innate inflammatory circuits that can collectively induce Th2 immune
responses. In an attempt to have a better understanding of the role of carbohydrates in the recognition and uptake of
allergens by the innate immune system, we defined common glycosylation patterns in major allergens. This was done using
labelled lectins and showed that allergens like Der p 1 ( Dermatophagoides pteronyssinus group 1), Fel d 1 ( Felis domisticus),
Ara h 1 ( Arachis hypogaea), Der p 2 ( Dermatophagoides pteronyssinus group 2), Bla g 2 ( Blattella germanica) and Can f 1
( Canis familiaris) are glycosylated and that the main dominant sugars on these allergens are 1–2, 1–3 and 1–6 mannose.
These observations are in line with recent reports implicating the mannose receptor (MR) in allergen recognition and uptake
by DCs and suggesting a major link between glycosylation and allergen recognition. We then looked at TSLP (Thymic
Stromal Lymphopoietin) cytokine secretion by lung epithelia upon encountering natural Der p 1 allergen. TSLP is suggested
to drive DC maturation in support of allergic hypersensitivity reactions. Our data showed an increase in TSLP secretion by
lung epithelia upon stimulation with natural Der p 1 which was carbohydrate dependent. The deglycosylated preparation of
Der p 1 exhibited minimal uptake by DCs compared to the natural and hyperglycosylated recombinant counterparts, with
the latter being taken up more readily than the other preparations. Collectively, our data indicate that carbohydrate
moieties on allergens play a vital role in their recognition by innate immune cells, implicating them in downstream
deleterious Th2 cell activation and IgE production

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- by Farouk Shakib and +1
  Mohamed Emara
- •
- 11
  Immunology, Allergy (Biomedicine), Dendritic cell Biology, Innate immunity

d-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor Induces Stable FimH Modifications

Urinary tract infections (UTIs) are mainly caused by uropathogenic Escherichia coli (UPEC). Acute and recurrent UTIs are commonly treated with antibiotics, the efficacy of which is limited by the emergence of antibiotic resistant strains. The natural sugar d-mannose is considered as an alternative to antibiotics due to its ability to mask the bacterial adhesin FimH, thereby preventing its binding to urothelial cells. Despite its extensive use, the possibility that d-mannose exerts "antibiotic-like" activity by altering bacterial growth and metabolism or selecting FimH variants has not been investigated yet. To this aim, main bacterial features of the prototype UPEC strain CFT073 treated with d-mannose were analyzed by standard microbiological methods. FimH functionality was analyzed by yeast agglutination and human bladder cell adhesion assays. Our results indicate that high d-mannose concentrations have no effect on bacterial growth and do not interfere with the activity of different antibiotics. d-mannose ranked as the least preferred carbon source to support bacterial metabolism and growth, in comparison with d-glucose, d-fructose, and l-arabinose. Since small glucose amounts are physiologically detectable in urine, we can conclude that the presence of d-mannose is irrelevant for bacterial metabolism. Moreover, d-mannose removal after long-term exposure did not alter FimH's capacity to bind to mannosylated proteins. Overall, our data indicate that d-mannose is a good alternative in the prevention and treatment of UPEC-related UTIs.

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Crystallization and initial X-ray diffraction studies of the flavoenzyme NAD(P)H:(acceptor) oxidoreductase (FerB) from the soil bacterium Paracoccus denitrificans

PASTA subunits ($70 amino acids) are specific to bacterial serine/threonine kinases and to penicillin-binding proteins (PBPs) and are involved in the synthesis of peptidoglycan. The human pathogen Staphylococcus aureus contains a serine/threonine kinase, Stk1, which plays a major role in virulence. A recombinant His-tagged portion of the extracellular domain of Stk1 containing three PASTA subunits has been crystallized using zinc sulfate as a crystallizing agent. The crystals belonged to the tetragonal space group P4 1 22, with unit-cell parameters a = 68.0, b = 68.0, c = 158.1 Å . Structure determination by the MAD method is now in progress.

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Recognition of the Major Cat Allergen Fel d 1 through the Cysteine-rich Domain of the Mannose Receptor Determines Its Allergenicity

Dendritic cells are professional antigen-presenting cells that are specialized in antigen uptake and presentation. Allergy to cat has increased substantially in recent years and has been shown to be positively associated with asthma. We have recently shown that the mannose receptor (MR), a C-type lectin expressed by dendritic cells, recognizes various glycoallergens from diverse sources and is involved in promoting allergic responses to a major house dust mite allergen in vitro. Here we investigated the potential role of MR in allergic responses to Fel d 1, a major cat allergen. Fel d 1 binding to MR was confirmed by ELISA. Using blocking, gene silencing (siRNA) experiments, and MR knockout (MR ؊/؊) cells, we have demonstrated that MR plays a major role in internalization of Fel d 1 by human and mouse antigen-presenting cells. Intriguingly, unlike other glycoallergens, recognition of Fel d 1 by MR is mediated by the cysteine-rich domain, which correlates with the presence of sulfated carbohydrates in natural Fel d 1. WT and MR ؊/؊ mice were used to study the role of MR in allergic sensitization to Fel d 1 in vivo. MR ؊/؊ mice sensitized with cat dander extract and Fel d 1 produced significantly lower levels of total IgE, Fel d 1-specific-IgE and IgG1, the hallmarks of allergic response, compared with WT mice. Our data show for the first time that Fel d 1 is a novel ligand of the cysteine-rich domain of MR and that MR is likely to play a pivotal role in allergic sensitization to airborne allergens in vivo.

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- by H. Sewell
- •
- 17
  Asthma, Dendritic cell Biology, Biological Chemistry, Gene Silencing

Recognition of the major cat allergen Fel d 1 through the cysteine-rich domain of the mannose receptor determines its allergenicity.

Dendritic cells are professional antigen-presenting cells that are specialized in antigen uptake and presentation. Allergy to cat has increased substantially in recent years and has been shown to be positively associated with asthma. We have recently shown that the mannose receptor (MR), a C-type lectin expressed by dendritic cells, recognizes various glycoallergens from diverse sources and is involved in promoting allergic responses to a major house dust mite allergen in vitro. Here we investigated the potential role of MR in allergic responses to Fel d 1, a major cat allergen. Fel d 1 binding to MR was confirmed by ELISA. Using blocking, gene silencing (siRNA) experiments, and MR knock-out (MR(-/-)) cells, we have demonstrated that MR plays a major role in internalization of Fel d 1 by human and mouse antigen-presenting cells. Intriguingly, unlike other glycoallergens, recognition of Fel d 1 by MR is mediated by the cysteine-rich domain, which correlates with the presence of sulfated carbohydrates in natural Fel d 1. WT and MR(-/-) mice were used to study the role of MR in allergic sensitization to Fel d 1 in vivo. MR(-/-) mice sensitized with cat dander extract and Fel d 1 produced significantly lower levels of total IgE, Fel d 1-specific-IgE and IgG1, the hallmarks of allergic response, compared with WT mice. Our data show for the first time that Fel d 1 is a novel ligand of the cysteine-rich domain of MR and that MR is likely to play a pivotal role in allergic sensitization to airborne allergens in vivo.

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Crystallization and initial X-ray diffraction analysis of a mannose-binding lectin from champedak

Mannose-binding lectin from champedak (Artocarpus integer) is a homotetramer with a single-monomer molecular weight of 16 800 Da. Previous work has shown it to bind IgE and IgM, as well as being a mitogen of T cells in humans. Champedak mannose-binding lectin has successfully been used to detect altered glycosylation states of serum proteins. The protein was crystallized at 293 K in space group P2(1)2(1)2(1) (unit-cell parameters a = 76.89, b = 86.22, c = 95.37 angstrom) and the crystals diffracted to 2.0 angstrom resolution.

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- by Onn Haji Hashim
- •
- 4
  Lectins, Artocarpus Integer, Champedak, Mannose Binding

Mannose Binding

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