The long and winding road of Ascaris larval migration: the role of mouse models

Abstract

AbstractAscaris lumbricoides and Ascaris suum are helminth parasites of humans and pigs, respectively. The life cycle of Ascaris sets it apart from the other soil-transmitted helminths because of its hepato-tracheal migration. Larval migration contributes to underestimated morbidity in humans and pigs. This migration, coupled with a lack of a murine model in which the Ascaris parasite might complete its life cycle, has undoubtedly contributed to the neglected status of the ascarid. Our knowledge of the epidemiology of adult worm infections had led us to an enhanced understanding of patterns of infection such as aggregation and predisposition; however, the mechanisms underlying these complex phenomena remain elusive. Carefully controlled experiments in defined inbred strains of mice – with enhanced recovery of larvae in tandem with measurements of cellular, histopathological and molecular processes – have greatly enhanced our knowledge of the early phase of infection, a phase crucial to the success or failure of adult worm establishment. Furthermore, the recent development of a mouse model of susceptibility and resistance, with highly consistent and diverging Ascaris larval burdens in the murine lungs, represents the extremes of the host phenotype displayed in the aggregated distribution of worms and provides an opportunity to explore the mechanistic basis that confers predisposition to light and heavy Ascaris infection. Certainly, detailed knowledge of the cellular hepatic and pulmonary responses at the molecular level can be accrued from murine models of infection and, once available, may enhance our ability to develop immunomodulatory therapies to elicit resistance to infection.