Abstract
A plant-derived secretory component conferred protease-resistance to Shiga toxin-specific mammalian immunoglobulin A. The protease-resistance was functionally demonstrated by a toxin neutralization assay.
AbstractSection AbstractSecretory component (SC) is believed to play roles in such as the protease-resistance of secretory immunoglobulin A (SIgA), allowing it to function on mucosae. Although the use of a plant expression system for SIgA production has been increasing, it has not been sufficiently assessed as to whether heterologously expressed SC could functionally contribute to the protease-resistance of SIgA. Here, we reconstituted SIgA using plant-derived SC and tested for changes in vulnerability to protease challenge. With glutathione redox buffers, plant-derived SC and mammalian cell-derived dimeric IgA (dIgA) specific for Shiga toxin 1 (Stx1) efficiently formed SIgA. Prior ammonium sulfate precipitation of dIgA was also shown to be useful to enhance the formation of SIgA. The reconstituted SIgA was treated with two gastrointestinal proteases, pepsin and trypsin. After 2-h pepsin treatment, the signal from SIgA remained at 42% with plant-derived SC-reconstitution while that from dIgA remained at 12% without SC-reconstitution on western blot analysis. Similarly, the signal from SIgA remained at 74% with SC but that from dIgA remained at 36% without SC after 4-h trypsin treatment. Furthermore, an effect of SC-reconstitution of dIgA on pepsin-resistance was observed in a toxin neutralization assay involving Vero cells. These results indicated that the plant-derived SC could contribute to the production of orally applicable SIgA.
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Acknowledgements
We thank Mr. N.J. Halewood for language editing services.
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This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Numbers JP15H04660 and JP25670063 to YI as well as by a research grant from the University of Shizuoka.
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KN, YN, HK and YI conceived and designed experiments. KN, NM, YK, MM, TM, KS and SM performed experiments. KN, NM, KK and YI analyzed the data. KN and YI wrote the manuscript. All authors read the manuscript and consented to publication.
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Nakanishi, K., Mogi, N., Kikuchi, Y. et al. Plant-derived secretory component gives protease-resistance to Shiga toxin 1-specific dimeric IgA. Plant Mol Biol 106, 297–308 (2021). https://doi.org/10.1007/s11103-021-01151-x
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DOI: https://doi.org/10.1007/s11103-021-01151-x