Innate lymphoid cells integrate sensing and plasticity to control fungal infections

  • Cell Rep. 2026 Apr 20;45(4):117140. doi: 10.1016/j.celrep.2026.117140.
Irina Tsymala  1 ,  Philipp Penninger  1 ,  Filomena Nogueira  2 ,  Sabrina Jenull  3 ,  Trinh Phan-Canh  1 ,  Helena Brezovec  1 ,  Magdalena Teufl  1 ,  Sara Miranda  4 ,  Wilfried Ellmeier  5 ,  Nicole Boucheron  5 ,  Birgit Strobl  4 ,  Dagmar Gotthardt  6 ,  Veronika Sexl  6 ,  Karl Kuchler  7
Affiliations
  • 1. Max Perutz Labs Vienna, Department for Medical Biochemistry, Medical University of Vienna, Vienna Biocenter Campus, Vienna, Austria.
  • 2. Max Perutz Labs Vienna, Department for Medical Biochemistry, Medical University of Vienna, Vienna Biocenter Campus, Vienna, Austria; CCRI-St. Anna Children's Cancer Research Institute, Vienna, Austria.
  • 3. Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria.
  • 4. Centre of Biological Sciences, University of Veterinary Medicine Vienna, Vienna, Austria.
  • 5. Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, 1090 Vienna, Austria.
  • 6. Department of Biological Sciences and Pathobiology, Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.
  • 7. Max Perutz Labs Vienna, Department for Medical Biochemistry, Medical University of Vienna, Vienna Biocenter Campus, Vienna, Austria. Electronic address: [email protected].
PMID: 42054206 DOI: 10.1016/j.celrep.2026.117140
Abstract

Innate lymphoid cells (ILCs) are crucial regulators of tissue immunity. Here, we demonstrate that pulmonary ILCs can sense Fungal components, leading to their activation. Mechanistically, we identify Syk/p38-dependent signaling as one of the key drivers of ILC activation following Fungal challenges. Aspergillus fumigatus Infection reshaped this response in vivo, creating a cytokine milieu that promoted ILC3 induction. We identified interleukin (IL)-23, IL-1β, and TGF-β as drivers of ILC2 conversion and IL-23 and IL-1β as triggers for ILC1s obtaining an ILC3 phenotype in vitro. Moreover, adoptive ILC transfer into Rag2-/-Il2rg-/- mice restrained excessive inflammation, while ILCs lacking the intracellular non-receptor tyrosine kinase Tec showed enhanced ILC1 proliferation and reduced Fungal burden. Consequently, transfer of Tec-deficient ILCs leads to better survival by enhancing Antifungal immunity. These findings uncover hitherto unrecognized roles for ILCs as early modulators of Antifungal immunity. Hence, targeting Tec signaling in ILCs may offer a therapeutic strategy to enhance Antifungal immunity.

Keywords
Aspergillus; CP: immunology; CP: microbiology; Candida glabrata; Candida species; IL-17A; ILC plasticity; ILCs; Syk signaling; Tec kinase; antifungal immunity; aspergillosis; fumigatus; host defense; inflammation; innate immunity; innate lymphoid cells; mucosal immunity; pulmonary infection.
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