Maternal milk-derived lipids dictate neonatal macrophage phenotype and function.

Unique properties of neonatal macrophages play an important role in tissue regeneration and susceptibility to infections. We discovered that exposure to neonatal mouse serum is sufficient to convert adult mouse macrophages into the neonatal phenotype. Macrophages incubated with neonatal serum accumulated lipid droplets due to the high lipid content in neonatal serum. We hypothesized that maternal milk derived lipids may be responsible for the immunomodulatory properties of neonatal serum. Supporting this hypothesis, sera from cow milk-fed adult mice converted adult macrophages into a neonatal macrophage phenotype. These macrophage phenotypic changes increased adult mouse susceptibility to cutaneous Leishmania major challenge, with skin macrophages manifesting an M2-like phenotype and CD4+ T cells mounting diminished Th1 responses. These results highlight the importance of maternal milk-derived serum lipids in the emergence of M2-like phenotype of neonatal macrophages and may have therapeutic implications by formulating a diet with tailored lipid content depending on host's immunobiological needs.