Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells

Abstract

Background Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood. Methods This in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy. Results We found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects. Conclusions To our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT.

An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen

“…Subsequent coculture of OVA-IEC-DC and OVA-DC with allogenic naïve Th cells demonstrated differential functional polarizing outcomes of these DC. More conventional in vitro allergy models mostly do not include IEC ( 16 , 24 , 25 ), while the presence of IEC is important in the initiation of the allergic response ( 13 , 26 , 27 ). Interestingly, OVA-IEC-DC did not alter type 1 or type 2 related cytokine secretion by T-cells, while OVA-DC were capable of driving Th2 polarization as indicated by enhanced IL13 secretion and an increased percentage of IL13-expressing Th cells.…”

Mechanistic insights into silica nanoparticle–allergen interactions on antigen presenting cell function in the context of allergic reactions

“…The nature of allergen, together with the internalization process, can influence allergic sensitization. 29,34 We, thus, determined the differences in the endocytosis of allergen by moDCs when conjugated to nanoparticles. Initially, the stability of nanoparticle-allergen conjugates in suspension was tested by the blue silicomolybdic assay to ensure that the delivered dose was similar to the administered dose (Fig.…”