Papel protetor do receptor atípico de quimiocinas ACKR2 na ascaridíase larval experimental

Abstract

Human ascariasis is a globally distributed geohelminthosis that affects about 500 million people, impacting public health in endemic areas. This disease is strongly related to precarious socioeconomic conditions and basic sanitation. Ascaris spp. infection presents an acute phase characterized by hepatopulmonary migration of the larvae parasite, and a chronic phase, which occurs after establishment of adult worm in the small intestine. Larval migration through by host’s organs initiates an intense inflammatory response with participation of important inflammatory mediators such as cytokines and chemokines. Chemokines are small molecules that play an important role in leukocyte biology by regulating cell activation and recruitment by binding to its receptor on the target cell. The atypical chemokine receptor ACKR2, unlike conventional receptors, is able to bind to chemokines of the CC family, internalizing their ligands and regulating the levels of chemokines in extracellular environment. However, little is known about the role of this receptor in larval ascariasis. Therefore, the objective of this work is to study the role of ACKR2 receptor involved in experimental larval ascariasis. For this purpose, wild C57BL/6 WT and ACKR2 KO mice were subjected to evaluation of parasitic load, inflammatory response and pathophysiology in the primo and reinfection by A. suum. Our results suggest that the ACKR2 receptor has an important protective role in experimental larval ascariasis. Deficient mice for ACKR2 receptor have an increased leukocyte recruitment, increased protein exudate and hemorrhage, impaired lung function, and did not develop the typical mixed Th1/Th2/Th17 immune response, which was associated with greater tissue damage and greater parasitic burden when compared to WT animals. Therefore, this work indicates that the ACKR2 receptor is important in regulation of inflammation and protective immune response, participates in control of parasitic burden, innate immune response and pathophysiological processes after primo and reinfection by A. suum.