ILC2s govern imprinting of alveolar macrophage-mediated immune responses upon secondary helminth infection in the lung.

Hookworms migrate through the lung as part of their lifecycle, causing significant tissue damage that activates tissue-resident populations such as ILC2s. These drive type 2 immune responses critical for wound healing and the development of protective immunity. Monocyte-derived macrophages that seed the lung after infection are central effectors of these responses, but the cellular and molecular factors guiding their development and function remain poorly understood. We find that ILC2s and IL-4/IL-13-producing CD4+ T cells regulate alveolar macrophage populations during helminth infection. In their absence, anti-parasitic immunity is impaired during secondary infection and the expansion of type 2-polarized monocyte-derived alveolar macrophages (Mo-AMs) is diminished. While Mo-AMs highly expressed Arg1, this was not essential for development of immunity. Concomitant with a distinct metabolic and transcriptional profile, ILC2-induced Mo-AMs selectively upregulated arachidonate 15-lipoxygenase which promoted anti-parasitic responses in vitro. Our results identify ILC2s and Th2 cells as critical regulators of alveolar macrophage dynamics and function during helminth infection.