Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2–MyD88 signal pathway in dendritic cells and enhances Th2 immune responses

Eosinophil‐derived neurotoxin (EDN) is an eosinophil granule‐derived secretory protein with ribonuclease and anti‐viral activity. We have previously shown that EDN can induce the migration of dendritic cells (DCs). Here we report that EDN can activate myeloid DCs by triggering the TLR2/Myd88 signaling pathway, thus establishing EDN as an endogenous ligand of TLR2. EDN activates TLR2 independent of TLR1 or TLR6. EDN also enhances antigen‐specific Th2‐biased immune responses as evidenced by predominant production of antigen‐specific IL‐5 and IL‐13 as well as higher levels of IgG1 than IgG2a. Based on its ability to serve as a chemoattractant and activator of DCs, as well as the capacity to enhance antigen‐specific immune responses, we consider EDN to have the properties of an endogenous alarmin that alerts the adaptive immune system for preferential enhancement of antigen‐specific Th2 immune responses. (Funded in whole or in part with federal funds from the NCI, NIH, under contract N01‐CO‐12400).

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