Ageing and the cellular immune response in adult Drosophila melanogaster

Abstract

Senescence is the age-related progressive deterioration of physiological processes leading to an increased likelihood of death and is a phenomenon that occurs nearly universally throughout all the world’s organisms. This thesis initially investigated the impact of ageing on the adult Drosophila melanogaster cellular immune response and demonstrated that the cellular immune response in D. melanogaster adults did experience an age-dependent decline in function. There was a striking reduction in haemocyte ability to phagocytose foreign particles with up to 30% less phagocytosis occurring in four week old flies compared to one week olds. Haemocyte number also declined in female flies by up to 32% across these ages. An exploration into the mechanisms that could underlie these observed senescent declines in haemocyte number and function revealed that the age-dependent reduction in the circulating haemocyte population occurred regardless of whether flies were unharmed, wounded or infected. The loss of phagocytosis ability in haemocytes in ageing flies was shown to be a cell autonomous process; there was an equal age-dependent decline (~13%) in haemocyte phagocytic activity in both in vivo and ex vivo assays. However, an attempt to identify phagocytic receptor systems that drove senescence in haemocyte function was unsuccessful. The contribution of the cellular immune response in determining survival following a fungal infection was not conclusively demonstrated, however flies with reduced Dif expression had significantly increased pathogen susceptibility. Although pathogen resistance can decline due to immune senescence, disease defence may also be enhanced as an animal’s life progresses through the formation of immunological memories of prior microbial encounters. This thesis revealed that the cellular immune response in D. melanogaster provides a strong, broadly specific and relatively long-lasting immunological priming response. Haemocytes phagocytosed up to 33% more microbes per cell during a secondary encounter, and up to 50% more if flies had received two homologous primes. This was not general immune upregulation as a heterologous microbial encounter caused a reduction in the phagocytic ability of haemocytes compared to controls. The level of enhancement in the phagocytic ability of haemocytes also declined with the age of the fly, meaning that the ability to develop a primed response senesced. These results are unprecedented in Drosophila and challenge our conventional interpretation of immune senescence because individual immune history has been shown to shape later cellular immune responses. Ageing is a complex and variable process. Some of the differences observed in ageing rates between populations can be due to different selection pressures. Natural selection acts on genetic variation within a population to increase fitness whereas host-parasite interactions predominantly influence genes related to immune parameters. Many genes have pleiotropic effects as well as there being potential trade-offs between investment in longevity, reproduction and immunity. To explore potential genetic variation in immune and life history traits and whether variation in immune parameters negatively influenced other life history traits related to ageing, a panel of outcrossed genotypes of D. melanogaster were assessed. As the flies were derived from individuals originally sourced from a natural population, the results suggest that a striking amount of genetic variation in immune and life history traits is present in wild populations. However no significant correlations between genetic variation in ageing and genetic variation in investment in immunity were identified. Though, perhaps not surprisingly, no key biomarker of ageing in D. melanogaster was identified; this thesis has contributed some significant findings on the effects of ageing on adult D. melanogaster especially relating to their cellular immune response.