Of dogs and hookworms: man's best friend and his parasites as a model for translational biomedical research

Abstract

We present evidence that the dog hookworm (Ancylostoma caninum) is underutilised in the study of host-parasite interactions, particularly as a proxy for the human-hookworm relationship. The inability to passage hookworms through all life stages in vitro means that adult stage hookworms have to be harvested from the gut of their definitive hosts for ex vivo research. This makes study of the human-hookworm interface difficult for technical and ethical reasons. The historical association of humans, dogs and hookworms presents a unique triad of positive evolutionary pressure to drive the A. caninum-canine interaction to reflect that of the human-hookworm relationship. Here we discuss A. caninum as a proxy for human hookworm infection and situate this hookworm model within the current research agenda, including the various 'omics' applications and the search for next generation biologics to treat a plethora of human diseases. Historically, the dog hookworm has been well described on a physiological and biochemical level, with an increasing understanding of its role as a human zoonosis. With its similarity to human hookworm, the recent publications of hookworm genomes and other omics databases, as well as the ready availability of these parasites for ex vivo culture, the dog hookworm presents itself as a valuable tool for discovery and translational research.

Keywords: Ancylostoma caninum; Hookworm model; Human hookworm; Omics; Translational model.

Fig. 1

The human-hookworm-dog relationship is defined by a long association. Positive evolutionary pressure on canines has caused them to adapt to human environments. Hookworms have likely had conflicting immunogenic environments during cross infection events between human and dogs. In the ~14,000 years of association (conservative estimate) it is theoretically possible to have nearly 73,000 generations of hookworm in this timeframe

Fig. 2

Hookworm life-cycles. Life-cycle a Ova contained in infected faeces hatch in soil and larvae live freely for up to two moults. Third-stage larvae (L3) come in contact with skin and penetrate the epidermis. Migrating through the lymphatic and circulatory system they end up in the lung. Larvae mature en route to the upper gastrointestinal tract via the pharynx and become fifth-stage larvae in the duodenum. Once attached to the small intestine they feed, become mature to reproductive capacity and mate. Eggs produced by the female worm are then shed in faeces. Alternatively, the free-living larvae are capable of infection through the oral route. These organisms are capable in some cases of latent stage/hypobiosis and trans-mammary or placental transmission. Life-cycle b does not include oral transmission. Latent stage/hypobiosis and alternative transfection routes are not reported in these organisms