The role of lectins in allergic sensitization and allergic disease

Salazar, Fabián; Sewell, Herb F.; Shakib, F; Ghaemmaghami, Amir M.

doi:10.1016/j.jaci.2013.02.001

Cited by 48 publications

(52 citation statements)

References 110 publications

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“…The role of glycosylation in the recognition and uptake of allergens by the innate immune system through C-type lectin receptors was also shown to be important for the initiation of the allergic response [23]. In this study, we observed an O-glycosylation site made of a stretch of threonine residues in the N-terminus of Der p 23.…”

Section: Discussionmentioning

confidence: 59%

The House Dust Mite Major Allergen Der p 23 Displays O-Glycan-Independent IgE Reactivities but No Chitin-Binding Activity

Soh¹,

Mignon

Suratannon³

et al. 2015

Int Arch Allergy Immunol

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Background: The in-depth characterization of the recently identified house dust mite (HDM) major allergen Der p 23 requires the production of its recombinant counterpart because the natural allergen is poorly extractable from fecal pellets. This study aimed to provide a detailed physico-chemical characterization of recombinant Der p 23 (rDer p 23) as well as to investigate its IgE reactivity in a cohort of HDM-allergic patients from Thailand. Methods: Purified rDer p 23, secreted from recombinant Pichia pastoris, was characterized by mass spectrometry and circular dichroism analyses as well as for its chitin-binding activity. The IgE-binding frequency and allergenicity of Der p 23 were determined by ELISA and RBL-SX38 degranulation assays, respectively. Results: Purified intact rDer p 23 carried O-mannosylation and mainly adopted a random coil structure. Polyclonal antibodies to rDer p 23 can detect the corresponding natural allergen (nDer p 23) in aqueous fecal pellet extracts, suggesting that both forms of Der p 23 share common B-cell epitopes. Despite its homologies with chitin-binding proteins, both natural Der p 23 and rDer p 23 were unable to interact in vitro with chitin matrices. Of 222 Thai HDM-allergic patients tested, 54% displayed Der p 23-specific IgE responses. Finally, the allergenicity of rDer p 23 was confirmed by the degranulation of rat basophil leukemia cells. Conclusion: Our findings highlighted important levels of Der p 23 sensitizations in Thailand. Our study clearly suggested that rDer p 23 is likely more appropriate for HDM allergy component-resolved diagnosis than HDM extracts.

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Section: Discussionmentioning

confidence: 59%

The House Dust Mite Major Allergen Der p 23 Displays O-Glycan-Independent IgE Reactivities but No Chitin-Binding Activity

Soh¹,

Mignon

Suratannon³

et al. 2015

Int Arch Allergy Immunol

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“…In addition, we found a significant reduction in the expression of the C-type lectin receptors DC-SIGN and mannose receptor (MR) (Fig. 2B) - which are receptors involved in antigen recognition and uptake15 - suggesting a decrease in the endocytic capacity of these cells. Interestingly, we did not find significant differences in the LPS receptor complex i.e.…”

Section: Resultsmentioning

confidence: 93%

“…They possess high functional plasticity in response to external stimuli, which allows them to orchestrate adaptive immune responses by either promoting or suppressing T-cell responses. Antigen recognition and uptake in the periphery followed by migration to secondary lymphoid organs along with expression of co-stimulatory molecules and secretion of cytokines are the main features that enable DCs to stimulate naïve T cells or under specific micro-environmental conditions induce tolerance1415. Lipopolysaccharide (LPS) activates the TLR4 pathway that induces the release of pro-inflammatory cytokines and the induction of co-stimulatory molecules necessary to activate immune responses.…”

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confidence: 99%

The role of indoleamine 2,3-dioxygenase-aryl hydrocarbon receptor pathway in the TLR4-induced tolerogenic phenotype in human DCs

Salazar

Awuah

Negm

et al. 2017

Sci Rep

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A controlled inflammatory response is required for protection against infection, but persistent inflammation causes tissue damage. Dendritic cells (DCs) have a unique capacity to promote both inflammatory and anti-inflammatory processes. One key mechanism involved in DC-mediated immunosuppression is the expression of tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO). IDO has been implicated in diverse processes in health and disease but its role in endotoxin tolerance in human DCs is still controversial. Here we investigated the role of IDO in shaping DCs phenotype and function under endotoxin tolerance conditions. Our data show that TLR4 ligation in LPS-primed DCs, induced higher levels of both IDO isoforms together with the transcription factor aryl-hydrocarbon receptor (AhR), compared to unprimed controls. Additionally, LPS conditioning induced an anti-inflammatory phenotype in DCs - with an increase in IL-10 and higher expression of programmed death ligand (PD-L)1 and PD-L2 - which were partially dependent on IDO. Furthermore, we demonstrated that the AhR-IDO pathway was responsible for the preferential activation of non-canonical NF-κB pathway in LPS-conditioned DCs. These data provide new insight into the mechanisms of the TLR4-induced tolerogenic phenotype in human DCs, which can help the better understanding of processes involved in induction and resolution of chronic inflammation and tolerance.

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“…Binding of heavily mannosylated allergens (eg, from house dust mite and cockroach) to mannose receptor on human DCs attenuates Toll-like receptor 4–induced expression of the T cell–suppressive enzyme indoleamine 2,3-dioxygenase (IDO) and decreases production of the T H 1-differentiating cytokine IL-12p70 (Fig 1, A ). 84,85 The stability of protein folding can also modulate T H 2 responses. Recent work with mutant molecules of the major birch allergen Bet v 1 suggests that increased stability might favor delivery of allergen to the late endosomal compartment for efficient processing and consequent increased epitope density at the DC surface.…”

Section: Tslpmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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The role of lectins in allergic sensitization and allergic disease

Cited by 48 publications

References 110 publications

The House Dust Mite Major Allergen Der p 23 Displays O-Glycan-Independent IgE Reactivities but No Chitin-Binding Activity

The House Dust Mite Major Allergen Der p 23 Displays O-Glycan-Independent IgE Reactivities but No Chitin-Binding Activity

The role of indoleamine 2,3-dioxygenase-aryl hydrocarbon receptor pathway in the TLR4-induced tolerogenic phenotype in human DCs

Pathogenic CD4 + T cells in patients with asthma

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