Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Abstract: The L3-secreted Ancylostoma Secreted Protein-2 from the human hookworm Necator americanus (Na-ASP-2) has been selected as a candidate vaccine antigen in anticipation of clinical trials. Its crystal structure revealed that Na-ASP-2 has structural and charge similarities to CC-chemokines, suggesting that it might act as a chemokine mimic when released by the infective larvae during tissue migration. Using the air pouch model of acute inflammation, we found that Na-ASP-2 induced a significant leukocyte influx to the skin pouch, mostly comprised of neutrophils (60%) and monocytes (30%) that was transient and resolved in 24h. Other hookworm larval proteins did not cause any inflammatory leukocytes to migrate into air pouches. In vitro chemotaxis assays confirmed our results and demonstrated that leukocyte migration was a direct effect of Na-ASP-2 exposure and not caused by other molecules released by host cells in the inflammatory microenvironment or by the expression vector. [Copyright &y& Elsevier]