Immune surveillance on the insect body surface recognizes a pathogen-derived fungal protease to activate defenses

Immune systems must distinguish between pathogens and commensals to mount effective responses. However, how hosts discriminate among fungi at surface barriers is largely unknown. Here, we report a surveillance mechanism on the locust body surface that couples general fungal recognition with pathogen-specific activation. The host immulectin-1 (IML1) binds surface-exposed fungal mannans, but immune activation requires cleavage by fungal protease SP28 to release bioactive peptide. The protease is found in most fungi, but high evolutionary divergence confers its host-specific activity. Disrupting the IML1-SP28 interaction, either by deleting fungal SP28, silencing host IML1, or blocking IML1 with excess mannan, abrogates immune responses and accelerates host mortality. This protease-gated checkpoint suggests an evolutionarily conserved principle in insect-fungal interactions, with potential implications for developing novel biopesticides and antifungal agents.