Insects fight low-dose infections with terminal investment, not innate immunity

Though the innate immune system is considered to be the primary defence promoting survival against pathogenic microbes, non-immunological strategies may provide cost-effective responses against ubiquitous low-dose infections. However, research using model systems has yet to develop a framework for systematically varying topical exposure doses, much less for examining how hosts mitigate the fitness costs associated with immune deployment. Here, we demonstrate that insects respond to low-dose infections with terminal investment. Female fruit flies, Drosophila melanogaster, have higher egg-to adult viability and lower survival when exposed to low-dose or sexually transmitted infections of an endemic fungus, Aspergillus austwickii. We identify Turandot C (TotC), a humoral stress response gene in insects, as the first non-immunological regulator of fecundity compensation. Strikingly, TotC-mediated fecundity compensation imposes negligible lifetime fitness costs, whereas expression of the canonical immune gene Dorsal-related immunity factor (Dif) triggers reproductively costly antagonistic pleiotropy. Contrary to foundational ecological theory, we show that terminal investment arises from immediate survival-reproduction trade-offs, not truncated reproductive potential. Our findings reveal that adaptive evolution of innate immunity is constrained by classical fitness trade-offs in response to ubiquitous low-dose infections, which permits the evolution of mechanisms in which the host strategically surrenders to the pathogen. Our study refines how we conceptualise host-pathogen evolutionary conflicts and underscores a need to understand how immunosuppression evolves in hosts under ecologically prevalent low-dose infections.