The Immunology Of Polyparasitism: How Underlying Chronic Worm Infections Affect Immune Responses To Veterinary Parasites

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Concurrent infections caused by multiple microbes are known as ‘polyparasitisms’ and are responsible for increased losses due to infectious diseases in domestic livestock and wildlife. Most of our current knowledge of immunity to infections has been generated from studies using simplified mono-infection models. My overall research goal is to discover how the host immune system interacts with parasites in polyparasitic environments within animals. The host immune response can be considered in two phases. The first, the innate response, is immediate, non-specific, and short-lived. The second, the adaptive response, is delayed but more specific, generating ‘immune memory’, a process by which the immune system can recognise an infection more effectively the second time. However, although the innate response is short-lived, it influences the nature of the ensuing adaptive response. Our central hypothesis is that underlying chronic worm infections strongly disrupt innate immune responses to other pathogens, therefore significantly altering disease dynamics in the context of polyparasitism. The aims of this research program are: 1. To employ complex polyparasitism models in animals, thus helping translate findings to the natural world. 2. To characterise how underlying chronic infections disrupt innate host immune responses to new parasitic infections. 3. To determine whether these altered host immune responses modify the parasite itself. I am most interested in two types of veterinary parasites: intestinal worms and single-celled coccidians. Intestinal worms cause chronic infections that strongly alter the host immune systems such that hosts are more likely to become infected with another parasite. Indeed, most animals infected with intestinal worms are co-infected, especially since effectively treating worms is extremely difficult. Few veterinary drugs are available to treat parasitic worms, and drug-resistance is an increasing problem in domestic animals. The coccidian Toxoplasma gondii is a parasite found in most types of mammals, which causes significant economic losses to the livestock industry. Both worms and T. gondii are common in Canada where they cause significant disease burden and are often observed together in the same organism. As such they represent appropriate models for studying ‘real-world’ immune responses in the context of polyparasitism. Polyparasitism studies with intestinal worms and T. gondii have already shown that the immune memory to T. gondii is less effective when worms are present. However, the underlying mechanisms remain obscure. My specific objectives in the five year period of this NSERC discovery grant are: 1. To develop a relevant mouse model of parasitic worm/T. gondii polyparasitism, representative of real-world dynamics, that models these infections in domestic animals or animals in the natural environment. 2. To characterize the mechanisms by which veterinary parasitic worms impair host innate immunity to T. gondii infection. I will focus on two types of innate immune cell: Natural Killer (NK) and NKT cells, both known to produce molecules required to resolve T. gondii infection. 3. To assess how chronic worm infection in animals modifies T. gondii virulence. The studies address the fundamental questions of host-parasite interactions, in the real-world setting of polyparasitism. The knowledge to be generated is of broad biological interest, and carries significant translational potential. In light of our lack of effective veterinary treatments/vaccines for these infections and our limited understanding of disease dynamics in natural environments, a better understanding of host immunity to polyparasitism may have a profound impact on our future veterinary disease management strategies.