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Resistance of parvalbumin to gastrointestinal digestion is required for profound and long-lasting prophylactic oral tolerance.

ABSTRACT: BACKGROUND:Early introduction of food allergens into children's diet is considered as a strategy for the prevention of food allergy. The major fish allergen parvalbumin exhibits high stability against gastrointestinal digestion. We investigated whether resistance of carp parvalbumin to digestion affects oral tolerance induction. METHODS:Natural Cyp c 1, nCyp c 1, and a gastrointestinal digestion-sensitive recombinant Cyp c 1 mutant, mCyp c 1, were analyzed for their ability to induce oral tolerance in a murine model. Both antigens were compared by gel filtration, circular dichroism measurement, in vitro digestion, and splenocyte proliferation assays using synthetic Cyp c 1-derived peptides. BALB/c mice were fed once with high doses of nCyp c 1 or mCyp c 1, before sensitization to nCyp c 1. Immunological tolerance was studied by measuring Cyp c 1-specific antibodies and cellular responses by ELISA, basophil activation, splenocyte proliferations, and intragastric allergen challenge. RESULTS:Wild-type and mCyp c 1 showed the same physicochemical properties and shared the same major T-cell epitope. However, mCyp c 1 was more sensitive to enzymatic digestion in vitro than nCyp c 1. A single high-dose oral administration of nCyp c 1 but not of mCyp c 1 induced long-term oral tolerance, characterized by lack of parvalbumin-specific antibody and cellular responses. Moreover, mCyp c 1-fed mice, but not nCyp c 1-fed mice developed allergic symptoms upon challenge with nCyp c 1. CONCLUSION:Sensitivity to digestion in the gastrointestinal tract influences the capacity of an allergen to induce prophylactic oral tolerance.

SUBMITTER: Freidl R

PROVIDER: S-EPMC7065025 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Resistance of parvalbumin to gastrointestinal digestion is required for profound and long-lasting prophylactic oral tolerance.

Freidl Raphaela R Gstöttner Antonia A Baranyi Ulrike U Swoboda Ines I Stolz Frank F Focke-Tejkl Margarete M Wekerle Thomas T van Ree Ronald R Valenta Rudolf R Linhart Birgit B

Allergy 20191003 2

<h4>Background</h4>Early introduction of food allergens into children's diet is considered as a strategy for the prevention of food allergy. The major fish allergen parvalbumin exhibits high stability against gastrointestinal digestion. We investigated whether resistance of carp parvalbumin to digestion affects oral tolerance induction.<h4>Methods</h4>Natural Cyp c 1, nCyp c 1, and a gastrointestinal digestion-sensitive recombinant Cyp c 1 mutant, mCyp c 1, were analyzed for their ability to ind ...[more]

PMID: 31325321

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Project description:Heatwaves are a regular occurrence in Australia, and are predicted to increase in intensity and duration in the future. These changes may elevate temperatures inside lizard nests, shortening the incubation period, so that hatchlings are more likely to emerge during heatwaves. Potentially, developmental plasticity or heat hardening could buffer hatchings from future warming. For example, higher incubation temperatures could shift critical thermal maxima upwards, enabling lizards to withstand higher temperatures. To investigate whether developmental plasticity affects hatchling thermal tolerance, we incubated eggs of the velvet gecko Amalosia lesueurii under two fluctuating incubation treatments to mimic current (mean=24.3°C, range 18.4-31.1°C) and future 'hot' (mean=28.9°C, range 19.1-38.1°C) nest temperatures. We maintained the hatchlings under identical conditions, and measured their thermal tolerance (CTmax) aged 14 days and 42 days. We then released hatchlings at field sites, and recaptured individually marked lizards aged 6 months, to determine whether incubation induced shifts in thermal tolerance were transitory or long-lasting. We found that at age 14 days, hatchlings from hot-temperature incubation had higher CTmax [mean=39.96±0.25°C (s.d.)] than hatchlings from current-temperature incubation [mean=39.70±0.36°C (s.d.)]. Hatchlings from the current-incubation treatment also had significantly higher heat hardening capacity [mean=0.79±0.37°C (s.d.)] than hatchlings from hot-temperature incubation treatment [mean=0.47±0.17°C (s.d. )]. However, both of these incubation-induced effects did not persist into later life. By contrast, incubation treatment had significant and long-lasting effects on the cold tolerance of hatchlings. At age 14 days, current-incubated hatchlings tolerated colder temperatures [CTmin=11.24±0.41°C (s.d.)] better than hot-incubated hatchlings [CTmin=14.11±0.25°C (s.d.)]. This significant difference in cold tolerance persisted into the juvenile life stage, and was present in 6-month-old lizards that we recaptured from field sites. This finding indicates that upward shifts in cold tolerance caused by higher incubation temperatures might affect overwinter survival of lizards, but field studies linking fitness to thermal tolerance are necessary to test this idea. Overall, our results suggest that developmental plasticity for heat tolerance is unlikely to buffer lizard populations from higher temperatures.

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Resistance of parvalbumin to gastrointestinal digestion is required for profound and long-lasting prophylactic oral tolerance.

Publications

Resistance of parvalbumin to gastrointestinal digestion is required for profound and long-lasting prophylactic oral tolerance.

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