Invasive pulmonary aspergillosis causes substantial mortality in immunocompromised individuals. Recognition of Aspergillus fumigatus by the host immune system leads to activation of the inflammasome, which provides protection against infection. However, regulation of inflammasome activation at the molecular level is poorly understood. Here, we describe two distinct pathways that coordinately control inflammasome activation during A.fumigatus infection. The C-type lectin receptor pathway activates both MAPK and NF-κB signalling, which leads to induction of downstream mediators, such as the transcription factor IRF1, and also primes the inflammasomes. Toll-like receptor signalling through the adaptor molecules MyD88 and TRIF in turn mediates efficient activation of IRF1, which induces IRGB10 expression. IRGB10 targets the fungal cell wall, and the antifungal activity of IRGB10 causes hyphae damage, modifies the A.fumigatus surface and inhibits fungal growth. We also demonstrate that one of the major fungal pathogen-associated molecular patterns, β-glucan, directly triggers inflammasome assembly. Thus, the concerted activation of both Toll-like receptors and C-type lectin receptors is required for IRF1-mediated IRGB10 regulation, which is a key event governing ligand release and inflammasome activation upon A.fumigatus infection.

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We thank members of the Kanneganti lab, the St. Jude Children’s Hospital Veterinary Pathology Core, Macromolecular Synthesis Core and Electron Microscopy Core. Images were acquired at the SJCRH Cell & Tissue Imaging Center, which is supported by SJCRH and NCI P30 CA021765–35. Work from our laboratories is supported by the US NIH (AI101935, AI124346, AR056296 and CA163507 to T.-D.K.) and the American Lebanese Syrian Associated Charities (to T.-D.K.). M.Y. is supported by the Research Program on Emerging and Re-emerging Infectious Diseases (18fk0108047h0002) and Japanese Initiative for Progress of Research on Infectious Diseases for Global Epidemic (18fm0208018h0002) from the Agency for Medical Research and Development.

Author information


  1. Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    • Benoit Briard
    • , Rajendra Karki
    • , R. K. Subbarao Malireddi
    • , Anannya Bhattacharya
    • , David E. Place
    • , Jayadev Mavuluri
    •  & Thirumala-Devi Kanneganti
  2. Cellular Imaging Shared Resource, St. Jude Children’s Research Hospital, Memphis, TN, USA

    • Jennifer L. Peters
  3. Animal Resources Center and the Veterinary Pathology Core, St. Jude Children’s Research Hospital, Memphis, TN, USA

    • Peter Vogel
  4. Department of Immunoparasitology, Research Institute for Microbial Diseases, Laboratory of Immunoparasitology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan

    • Masahiro Yamamoto


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B.B., R.K., R.K.S.M., J.M., A.B., D.E.P. and J.L.P. performed the experiments. B.B., R.K., R.K.S.M., P.V., M.Y. and T.-D.K. analysed the data. B.B., A.B. and R.K. wrote the paper. T.-D.K. oversaw the project and funding.

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The authors declare no competing interests.

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Correspondence to Thirumala-Devi Kanneganti.

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