Fig. 1
Bacterial-derived inosine induces NFIL3-T cell-dependent antiviral immunity in early life. Gut microbiome-derived inosine and consequent elevated systemic levels of inosine (e.g., plasma and lung) activate the adenosine 2 A receptors (A2AR) on CD8⁺ T cells. Receptor activation enhances cAMP response element-binding protein (CREB) activation and increases the expression of the transcription factor nuclear factor interleukin 3 (NFIL3). NFIL3 represses the transcription of transcription factor 7 (Tcf7) and lymphoid enhancer-binding factor 1 (Lef1). This promotes CD8⁺ T cell proliferation, effector differentiation, IFN-γ production, and supports the development of tissue resident memory (TRM) cells in the lung. Collectively, this strengthens antiviral immunity and protects newborns from influenza infection. a Depicting sufficient inosine abundance leading to efficient influenza virus control. b Depicting reduced inosine abundance, leading to impaired influenza virus control. Figure was created with BioRender, Affinity Designer 2 and Photoshop
