Abstract
Beta-lactoglobulin (BLG)-derived peptides may facilitate oral tolerance to whey and prevent cow's milk allergy (CMA). Loading of BLG-peptides in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Pep-NP) may improve this. Here we studied the uptake of NP and the capacity of NP and Pep-NP to activate bone marrow dendritic cells (BMDC). Furthermore, CMA prevention was evaluated by orally exposing three-week-old female C3H/HeOuJ mice to Pep-NP, NP or free peptides (PepMix) for 6 days before oral sensitization with whole whey protein and effects on the spleen and small intestine lamina propria (SI-LP) were studied. In BMDC, NP and Pep-NP enhanced CD40 expression and IL-6 and TNF-α secretion, while tended to decrease CD80 expression and prevented PepMix-induced IL-12 secretion. In vivo, oral exposure to Pep-NP, but not NP or PepMix, prior to whey sensitization tended to partially prevent the acute allergic skin response to whole whey protein. Splenocytes of NP-pre-exposed mice secreted increased levels of whey-specific IL-6, but this was silenced in Pep-NP-pre-exposed mice which also showed reduced TNF-α and IFN-γ secretion. In the SI-LP, Pep-NP pre-exposure reduced the CD4+ T cell frequency in CMA mice compared to PBS pre-exposure. In addition, while NP increased whey-specific IL-6 secretion in the SI-LP, Pep-NP did not and maintained regulatory TGF-β secretion. This study presents a proof-of-concept that PLGA nanoparticles facilitate the capacity of BLG peptides to suppress the allergic response to whole whey protein. Hence, PLGA nanoparticles may be further developed as an adjunct strategy for BLG-peptide-based oral tolerance induction and CMA prevention.
Highlights
Cow's milk allergy (CMA) is the most prevalent food allergy in children younger than 5 years (Koletzko et al, 2012; Venter and Arshad, 2011)
To investigate the effect of peptide-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles on dendritic cells (DC) activation in vivo, we studied the expression of co-stimulatory molecules on CD11c+MHC-II+F4/80- DC in the mesenteric lymph nodes (MLN) and small intestine lamina propria (SI-LP)
Three of the four BLG-derived peptides were successfully loaded in PLGA nanoparticles, of which peptide 3 and 4 were released in a biphasic manner as expected for PLGA particles (Makadia and Siegel, 2011), indicating successful encapsulation with a sustained release profile
Summary
Cow's milk allergy (CMA) is the most prevalent food allergy in children younger than 5 years (Koletzko et al, 2012; Venter and Arshad, 2011). Even though most children outgrow CMA by developing tolerance, they have an increased risk of developing other atopic disorders later in life, such as asthma, rhinoconjunctivitis or functional gastrointestinal disorders (Nissen et al, 2013; Saps et al, 2011). Whole allergen is introduced only after 4 months of age (Du Toit et al, 2015), which encourages the search for other, safer, strategies that would allow active intervention in the first months of life when breastfeeding is not possible
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