Abstract
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.
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Acknowledgements
We thank the Analytical and Testing Center, Chongqing University, for assistance with electron microscopy. This study was supported by the Technology Innovation and Application Development Project of Chongqing (CSTB2023TIAD-KPX0045), the Fundamental Research Funds for the Central Universities (2025CDJ-IAISYB-023, 2024CDJXY016), High-end Foreign Experts Introduction Program (G2023165012L), Fund for International Cooperation and Exchange of the National Natural Science Foundation of China (32111530121) and the Royal Society’s (London) International Exchange Program (IEC\NSFC\201298).
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Li, J., Xiao, Q., Ligoxygakis, P. et al. Immune surveillance on the insect body surface recognizes a pathogen-derived fungal protease to activate defenses. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72836-4
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DOI: https://doi.org/10.1038/s41467-026-72836-4
