Maternal milk-derived lipids dictate neonatal macrophage phenotype and function

Area of Science:

• Immunology
• Macrophage Biology
• Neonatal Development

Background:

• Neonatal macrophages possess unique properties crucial for tissue regeneration and immune responses.
• Adult macrophages differ significantly from neonatal ones, impacting their role in health and disease.
• Understanding the factors that induce neonatal macrophage phenotypes is vital for immune modulation.

Purpose of the Study:

• To investigate the role of neonatal serum components in inducing a neonatal macrophage phenotype in adult macrophages.
• To determine if lipids, particularly those derived from maternal milk, are responsible for these phenotypic changes.
• To assess the impact of these induced phenotypic changes on susceptibility to parasitic infections.

Main Methods:

• Incubation of adult mouse macrophages with neonatal mouse serum.
• Analysis of lipid droplet accumulation in macrophages.
• Feeding adult mice cow's milk and analyzing their serum's effect on macrophages.
• Challenging mice with *Leishmania major* and evaluating immune responses (macrophage phenotype, T cell responses).

Main Results:

• Exposure to neonatal serum induced a neonatal macrophage phenotype in adult macrophages, characterized by lipid droplet accumulation.
• High lipid content in neonatal serum was identified as a key factor.
• Sera from adult mice fed cow's milk mimicked the effect of neonatal serum.
• Induced M2-like macrophage phenotype in adult mice increased susceptibility to cutaneous *Leishmania major* infection, with diminished Th1 responses.

Conclusions:

• Maternal milk-derived lipids in serum are sufficient to confer a neonatal macrophage phenotype onto adult macrophages.
• This lipid-induced phenotype alters immune responses, increasing susceptibility to certain infections.
• Dietary lipid modulation, informed by maternal milk composition, may offer therapeutic strategies for immune regulation.