Almost a quarter of the world’s population suffer from soil-transmitted helminth infection, with the majority prevailing in impoverished regions such as eastern Asia, sub-Saharan Africa and the Americas. Levels of infection are also high amongst aboriginal Australian’s living in the Northern Territories, for those living in the Torres Strait Islands and in Papua New Guinea, due to a lack of sanitation, increasing anti-helminthic resistance in livestock and limited access to medical care. In addition, helminth parasites generally establish long-term infections, reflecting their ability to drive a new physiological and immunological status within their host. The two helminths we use in the lab, Nippostrongylus brasiliensis and Heligmosomoides polygyrus, are natural rodent parasites which are closely related to human hookworm, and thus represent an effective model for studying host-parasite interactions. The Intestinal Immunology Laboratory aims to understand how our commensal bacteria (microbiota) and soil-transmitted helminths interact with the mammalian intestinal immune system, driving immunomodulation or inducing protection within their host. We investigate changes in intestinal immunity, physiology and wound repair/tissue regeneration. In a natural setting, both humans and animals can be regularly exposed to helminth infections throughout their lives. The frequent exposure to infection is in marked contrast to many laboratory studies of parasite infection, in which we often administer a single bolus infection at either one or two intervals, using doses which are not necessarily physiological or reflective of field conditions. The overall aim of this project is to further understand the role of the immune response in repeated, low-dose “trickle” infections, as this would more faithfully recapitulate exposure and infection that we observe in humans and livestock. The findings of this project may therefore result in a more robust body of work which can be readily translated to humans. Human helminth infection can go undetected for a number of months or years, meaning that the timing of initial infection is often missed or incorrect when collecting field data. By conducting these trickle infections in mice, we can track the immune response to repeated low-dose infection from the onset, and assess the impact on multiple cells and tissues that the parasite interacts with during its lifecycle both in vitro and in vivo. This will require optimisation for both dose and timing, as well as generating an immune profile for infection by two different helminth parasites using a large variety of immunological methods including microscopy, RNA analysis and flow cytometry.
helminth, trickle infection, anti-parasite responses, type-2 immunity
Central Clinical School » Immunology and Pathology
Alfred Centre, The Alfred Hospital