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

C V Holland

doi:10.1017/s0031182021000366

Abstract

Ascaris 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.

Highlights

Ascaris lumbricoides, the human roundworm, and its porcine counterpart Ascaris suum are lumen-inhabiting adult nematode worms that produce large numbers of eggs that pass into the environment
In an Ascaris mouse model, a significant reduction in body weight was observed in mice that received higher doses of Ascaris ova, indicating that larval migration and accumulation of larvae in the lungs has a significant impact upon host body condition even in abnormal hosts that sustain only the migratory and tissue-resident phases of infection (Lewis et al, 2009)
Following on from the proteomic work that focused upon A. suum only (Deslyper et al, 2016, 2019b) and the quantitative comparative studies on the larval migration of A. suum and A. lumbricoides (Deslyper et al, 2020), it was concluded that it was important, as a step, to determine which immune cells are activated in the liver and whether these cells differed between the two strains of mice and the two species of ascarid

Summary

Introduction

The human roundworm, and its porcine counterpart Ascaris suum are lumen-inhabiting adult nematode worms that produce large numbers of eggs that pass into the environment. In an Ascaris mouse model, a significant reduction in body weight was observed in mice that received higher doses of Ascaris ova, indicating that larval migration and accumulation of larvae in the lungs has a significant impact upon host body condition even in abnormal hosts that sustain only the migratory and tissue-resident phases of infection (Lewis et al, 2009).

Results

Conclusion