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<p>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 <i>SP28</i>, silencing host <i>IML1</i>, 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月9日

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  • Jun Li,
  • Qi Xiao,
  • Petros Ligoxygakis,
  • Yuxian Xia

摘要

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.