Microbial metabolite facilitates virus control: inosine and T cells curb early-life influenza infection

The research by Stevens and colleagues shows that early-life disturbances of the microbiota, such as antibiotic exposure during pregnancy, reduce the transfer of key bacteria like Bifidobacterium and Lactobacillus to offspring. As a result, infant mice develop weakened CD8⁺ T cell responses to influenza A infection, suffer more severe disease, and remain less protected even later in life.

Mechanistic experiments identified NFIL3 as a key transcription factor regulating T cell differentiation. Microbiome-derived inosine activates the adenosine A₂A receptor–CREB–NFIL3 signaling pathway in T cells, enhancing their proliferation, effector differentiation, and interferon-γ production. Supplementation with inosine, or colonization with the inosine-producing bacterium Bifidobacterium pseudolongum, restored antiviral immunity and protected animals from influenza-induced weight loss and tissue damage.

The findings uncover a microbiome–metabolite–immune axis that shapes lifelong antiviral defense. They also highlight the potential of inosine-based or probiotic therapies to protect high-risk infants, such as those exposed to antibiotics or born preterm, from severe viral infections.

Reference:
Sevenich L., Le T.T., Mager L.F. Microbial metabolite facilitates virus control: inosine and T cells curb early-life influenza infection. Signal Transduction and Targeted Therapy (2025) 10:308. DOI: 10.1038/s41392-025-02417-2