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 antiviral activity. We have previously shown that EDN can induce the migration and maturation of dendritic cells (DCs). Here, we report that EDN can activate myeloid DCs by triggering the Toll-like receptor (TLR)2-myeloid differentiation factor 88 signaling pathway, thus establishing EDN as an endogenous ligand of TLR2. EDN activates TLR2 independently of TLR1 or TLR6. When mice were immunized with ovalbumin (OVA) together with EDN or with EDN-treated OVA-loaded DCs, EDN enhanced OVA-specific T helper (Th)2-biased immune responses as indicated by predominant production of OVA-specific interleukin (IL)-5, IL-6, IL-10, and IL-13, as well as higher levels of immunoglobulin (Ig)G1 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.
Yang
De
D
Basic Research Program, SAIC-Frederick, Inc., MD, USA. dyang@ncifcrf.gov
Chen
Qian
Q
Su
Shao Bo
SB
Zhang
Ping
P
Kurosaka
Kahori
K
Caspi
Rachel R
RR
Michalek
Suzanne M
SM
Rosenberg
Helene F
HF
Zhang
Ning
N
Oppenheim
Joost J
JJ
D000818:Animals; D003713:Dendritic Cells / Q000166:cytology; D047208:Eosinophil-Derived Neurotoxin / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology*; D005786:Gene Expression Regulation; D007107:Immune System; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D018418:Th2 Cells / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D009498:Neurotoxins; C495342:TLR2 protein, human; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D047208:Eosinophil-Derived Neurotoxin