Evolutionary ecology of parasite strategies for within-host survival

Abstract

Plasmodium parasites, the causal agents of malaria, engage in complex interactions with their hosts, however despite decades of research much of their life cycle remains unexplored. A deeper understanding of the strategies parasite have evolved to survive within, and exploit hosts, offers novel approaches for treating infections. By integrating tools from different fields within parasitology with an eco-evolutionary framework, I explore some of the strategies Plasmodium chabaudi parasites deploy within poorly studied aspects of their life cycle. Using this rodent malaria model, I first tested the relationship between host daily rhythms and the transition of parasites from developing in the liver to replication in the blood. In contrast to expectation, host circadian rhythms(i.e. feeding-fasting rhythms) do not influence the timing or the manner by which parasites begin the blood stage of their lifecycle. Moreover, how parasites undertake this critical step appears selectively neutral, suggesting that the rhythmicity in blood stage replication that is well-known in malaria parasites is rapidly established once in the blood. I then explored the ecology of sequestration (withdrawal from the blood to organs), a parasite strategy assumed to facilitate immune evasion and that is related to the manifestation of severe disease phenotypes, and potentially transmission. Specifically, I tested whether sequestration is scheduled to align with host rhythms driven by feeding-fasting or by photoperiod. I found little evidence for host rhythms affecting sequestration, or its consequences for replication. However, whether or not hosts experience disruption to their own rhythms influences sequestration in the lungs. Finally, I resolved controversy and conflicting reports concerning the role of innate immune responses on infection dynamics, especially during the establishment of infections. My comprehensive meta-analysis show that innate immune factors have only a minor impact on parasite replication in the blood. Overall, my thesis contributes to malaria knowledge by uncovering new aspects of parasite ecology and interactions with the host.