Milk osteopontin alters the infant microbiome to drive DC hematopoiesis and disease tolerance.

Milk-derived osteopontin (OPN) deficiency in neonatal mice increases susceptibility to severe respiratory infections by disrupting dendritic cell hematopoiesis.

• Why it matters: Understanding how breastfeeding protects infants from severe lower respiratory infections is crucial, as the mechanisms remain unclear, limiting potential therapeutic strategies.
• What they did: The study used neonatal mice to show that absence of milk OPN leads to impaired DC development in liver and lung, and that oral OPN, PLA, or rosiglitazone can restore DC hematopoiesis and disease tolerance through microbiome and chemokine pathways.
• The result: Findings reveal that milk OPN influences the microbiome and PPARγ signaling to promote lung immune cell development, offering insights into microbiome-host interactions that confer protection against respiratory disease.