Abstract: A full understanding of the immune response as a driver of host disease and pathogen evolution requires a quantitative account of its impact on parasite population dynamics. The complexity and redundancy of the immune system, together with the rapid pace of scientific progress in immunology, conspire to make mechanistic approaches both cumbersome and tentative. In this work, we use a top-down approach to quantify the birth and death processes shaping the dynamics of infections of the rodent malaria parasite, Plasmodium chabaudi, and the red blood cells (RBCs) it targets. We decompose the immune response into three components, each with a distinct effect on parasite and RBC vital rates, and quantify the relative contribution of each component to host disease and parasite density. Our analysis suggests that these components are deployed in a coordinated fashion to realize distinct resource-directed defense strategies that complement the killing of parasitized cells. By quantifying the impact of immunity on both parasite fitness and host disease, we reveal that phenomena often interpreted as immunopathology may in fact be beneficial to the host. Finally, we show that, across mice, the components of the host response are consistently related to each other, even when infections follow qualitatively different trajectories. This suggests the existence of simple rules that govern the immune system’s deployment.
Collins Conference Room
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Aaron King (University of Michigan)
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