Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Allergic diseases represent a significant burden in industrialized countries, but why and how the immune system responds to allergens remain largely unknown. Because many clinically significant allergens have proteolytic activity, and many helminths express proteases that are necessary for their life cycles, host mechanisms likely have evolved to detect the proteolytic activity of helminth proteases, which may be incidentally activated by protease allergens. A cysteine protease, papain, is a prototypic protease allergen that can directly activate basophils and mast cells, leading to the production of cytokines, including IL-4, characteristic of the type 2 immune response. The mechanism of papain's immunogenic activity remains unknown. Here we have characterized the cellular response activated by papain in basophils. We find that papain-induced IL-4 production requires calcium flux and activation of PI3K and nuclear factor of activated T cells. Interestingly, papain-induced IL-4 production was dependent on the immunoreceptor tyrosine-based activation motif (ITAM) adaptor protein Fc receptor γ-chain, even though the canonical ITAM signaling was not activated by papain. Collectively, these data characterize the downstream signaling pathway activated by a protease allergen in basophils.

Original publication




Journal article


Proc natl acad sci u s a

Publication Date





E4963 - E4971


allergen, basophil, signaling, Adaptor Protein Complex Subunits, Allergens, Animals, Basophils, Calcium Channel Blockers, Calcium Channels, Calcium Signaling, Cells, Cultured, Cysteine Proteinase Inhibitors, Gene Expression Regulation, Immunization, Interleukin-13, Interleukin-33, Interleukin-4, Interleukins, Leucine, MAP Kinase Signaling System, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, NFATC Transcription Factors, Papain, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Receptors, IgE, Receptors, IgG, Signal Transduction, Specific Pathogen-Free Organisms