Receptor for advanced glycation end-product (RAGE) modulates inflammation during feeding of tick, Haemaphysalis longicor

Abstract Ticks are notorious blood-sucking ectoparasites affecting both humans and animals, and serve as a unique vector of various deadly diseases. Here, we have shown the roles of the receptor for advanced glycation end-products (RAGE) during repeated infestations by the tick, Haemaphysalis longicornis using RAGE mice. In primary infestation, a large blood pool developed which was flooded with numerous RBC, especially during the rapid feeding phase of the tick both in wild type (wt) and RAGE mice. Very few inflammatory cells were detected around the zones of hemorrhage in the primary infestations. However, number of inflammatory cells gradually increased in the subsequent tick infestations and at the 3 infestations number of inflammatory cells reached to the highest level (350.3±16.8 cells/focus), and the site of attachment was totally occupied by the inflammatory cells in wild type (wt) mice whereas very few cells were detected at the ticks’ biting sites in RAGE mice. RAGE was highly expressed in the 3 infestation in wt mice. In the 3 infestation, infiltration of innate lymphoid cells type 2 (ILC2s), expression of S100A8 and S100B significantly increased at the biting sites of ticks in wt, but not in RAGE mice. Also, peripheral eosinophil counts significantly increased in wt but not in RAGE mice. Taken together, our study revealed that RAGE-mediated inflammation and eosinophils played crucial roles in the tick induced inflammatory reactions.