Innate lymphoid cells integrate sensing and plasticity to control fungal infections.

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.