Immunity: FOXO maintains defenses during famine

During times of energy shortage or stress, it is crucial to maintain immune defenses against opportunistic pathogens. In all species, innate immunity is the primary line of defense in barrier tissues. However, it is unclear how nutritional states influence innate immune responses. Becker et al. discovered that, when energy levels are low, the forkhead transcription factor FOXO directly upregulates antimicrobial peptides (AMP). FOXO is an important regulator of metabolism, stress resistance and aging, and elevates AMP production. AMPs destroy pathogens by perforating their cell walls or by binding to proteins that pathogens need to survive. In non-infected Drosophila, AMP induction is lost in foxo null mutants, but enhanced with FOXO overexpression. Additionally, FOXO is sufficient to induce AMP genes in immunocompromised mutant flies. Researchers also found that FOXO-dependent AMP regulation is evolutionarily conserved in humans. This novel discovery elucidates a mechanism by which an organism can maintain and strengthen its primary defense, especially during times of nutrient deprivation.