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

Milk-derived osteopontin protects neonatal mice against severe lower respiratory infections by supporting dendritic cell hematopoiesis in the developing liver and lung. Mice lacking milk OPN were predisposed to viral and bacterial sLRI; oral OPN raised Lactobacillaceae and serum 3-phenyllactic acid, a PPARγ agonist, and PLA or rosiglitazone restored lung DC hematopoiesis through CCL25-mediated progenitor recruitment. Depleting plasmacytoid DCs, neutralizing stem cell factor, or deleting airway epithelial Flt3L attenuated the effect.