<b>Fruit flies fight low dose infections by having more offspring</b>

Innate immune defences exhibit variable effectiveness, a phenomenon not yet fully understood. Recent research indicates that organisms may employ fundamentally different mechanisms to combat low-dose topical infections common in nature than severe infections. Here, we show that insects respond to low-dose topical infections by triggering terminal investment. Using simple methods for topical inoculations, we find that exposing fruit flies, Drosophila melanogaster, to low or sexually transmitted doses of the indigenous fungus Aspergillus austwickii boosts egg-to-adult viability, thereby maintaining lifetime reproductive output. By varying infection doses, we describe a pattern of correlations between reproductive success and mortality rate consistent with the threshold model of terminal investment. Quantitative analysis of age-dependent reproductive and mortality patterns reveals a misunderstanding of fundamental assumptions in life history theory: theories of senescence inadequately explain life history trade-offs induced by infections. Residual Reproductive Value may not necessarily be the evolutionary rationale underlying terminal investment. Our study shows that terminal investment involves an immediate trade-off between egg-to-adult viability and survival post-infection, rather than being driven by age-dependent trade-offs. The plasticity of life history traits in response to low-dose infections constrains the evolution of immunity, maintaining negative phenotypic correlations. Using the Gal4/UAS RNAi candidate gene knockdown approach, we compare the life history consequences of a canonical innate immune gene, Dorsal-related immunity factor. This comparison confirms that immune gene-mediated antagonistic pleiotropy drives insects to shift from reproductive to survival mechanisms of protection, depending on the mode of infection. Furthermore, we characterise a novel terminal investment mechanism encoded by Turandot C gene, which helps females minimise the costs of defence against the entomopathogenic fungus Metarhizium robertsii by shifting reproductive output post-infection. Our findings highlight the need for more research on common infections in nature to inform important non-immunological defences in a broader ecological context.