Immune serum-activated human macrophages coordinate with eosinophils to immobilize Ascaris suum larvae.

Abstract

Helminth infection represents a major health problem causing approximately 5 million disability-adjusted life years worldwide. Concerns that repeated anti-helminthic treatment may lead to drug resistance render it important that vaccines are developed but will require increased understanding of the immune-mediated cellular and antibody responses to helminth infection. IL-4 or antibody-activated murine macrophages are known to immobilize parasitic nematode larvae, but few studies have addressed whether this is translatable to human macrophages. In the current study, we investigated the capacity of human macrophages to recognize and attack larval stages of Ascaris suum, a natural porcine parasite that is genetically similar to the human helminth Ascaris lumbricoides. Human macrophages were able to adhere to and trap Asuum larvae in the presence of either human or pig serum containing Ascaris-specific antibodies and other factors. Gene expression analysis of serum-activated macrophages revealed that CCL24, a potent eosinophil attractant, was the most upregulated gene following culture with Asuum larvae in vitro, and human eosinophils displayed even greater ability to adhere to, and trap, Asuum larvae. These data suggest that immune serum-activated macrophages can recruit eosinophils to the site of infection, where they act in concert to immobilize tissue-migrating Ascaris larvae.