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When and how does pathogen-imposed selection favour increased host resistance?
There is abundant evidence for genetic variation in resistance, and of reduced host fitness following infection. Why are hosts not more resistant to infection.
There are numerous possible answers to this question, including costs of resistance and the existence of on-going host-parasite arms races. However, we are looking at other possible answers.
1. Resistance and virulence phenotypes may have a very large environmental component, washing out any genetic response to selection. Using the sterilising bacteria P. ramosa of Daphnia magna, we are looking at the effects of temperature, spore dose, maternal condition and resource availability on clone differences in infectivity and virulence. A very large environmental component may explain why parasite-induced sterilisation fails to select for increased host resistance, even though there is very considerable differences in resistance between clones.
2. Trade-offs between components of immunity. It may be that enhanced resistance against one pathogen would reduce resistance against another. We are particularly interested in the balancing act natural selection has to optimise is the generation of T-helper cell subsets appropriate for particular infections. Mounting the wrong sort of T-helper/cytokine response to a given parasite/pathogen can exacerbate pathology. The cytokines and effector mechanisms enabled by T-helper type 1 cells work best against intracellular bacteria, for example, whereas type 2-associated cytokines and effectors work best against intestinal nematodes. Immunopathology may result if the response is not tailored to the parasite. How does natural selection minimise pathology following co-infection by two or more parasites/pathogens that require different immune responses? We are developong quantitative systematic summary measures of T-helper cell responses in mice in order to test optimality models which predict how the verterbrate immune system should respond to co-infections which make conflicting demands on it.
Group members involved:
Current collaborators: Andrea
Graham, Gráinne Long, Judi
Allen, Tom Little.