Knoop, K. | bioRxiv Science

bioRxiv2024

EGF and IgA in maternal milk, donor milk and milk fortifiers in the Neonatal Intensive Care Unit setting

Human milk contains a variety of factors that positively contribute to neonatal health, including epidermal growth factor (EGF) and immunoglobulin A (IgA). When maternal milk cannot be the primary diet, maternal milk alternatives like donor human milk or formula can be provided. Donor human milk is increasingly provided to infants born preterm or low birth weight with the aim to supply immunological factors at similar concentrations to maternal milk. We sought to assess the concentrations of human EGF and IgA in the diet and stool of neonates between exclusive maternal milk, donor human milk, or formula-based diets. Using a prospective cohort study, we collected samples of diet and stool weekly from premature and low birth weight neonates starting at 10 days postnatal through five weeks of life while admitted to a neonatal intensive care unit (NICU). Compared to formula, there was significantly more EGF in both the milk and the stool of the infants fed human milk. Donor milk pooled from multiple donors contained similar concentrations of EGF and IgA to maternal milk, which was also significantly more compared to formula diets. Maternal milk fortified with fortifier derived from human milk contained significantly more EGF and IgA compared to unfortified maternal milk or maternal milk fortified with fortifier derived from bovine milk. Further analysis of human milk-derived fortifiers confirmed these fortifiers contained significant concentrations of EGF and IgA, contributing to an increased concentration of those factors when added to maternal milk compared to bovine milk-derived fortifiers. These findings illustrate how the choice of diet for a newborn, and even how that diet is modified through fortifiers or pasteurization before ingestion, impacts the beneficial biomolecules the infant receives from feeding.

immunology↗

bioRxiv2023

Streptococcus agalactiae and Escherichia coli Induce Distinct Effector γδ T Cell Responses During Neonatal Sepsis and Neuroinflammation

Neonates born prematurely are highly vulnerable to life-threatening conditions such as bacterial sepsis. Streptococcus agalactiae, also known as group B Streptococcus (GBS) and Escherichia coli are frequent causative pathogens of neonatal sepsis, however, it remains unclear if distinct sepsis pathogens induce differential adaptive immune responses. In the present study, we find that {gamma}{delta} T cells in neonatal mice rapidly respond to single-organism GBS and E. coli bloodstream infections and that these pathogens induce distinct activation and cytokine production from IFN-{gamma} and IL-17 producing {gamma}{delta} T cells, respectively. We also report differential reliance on {gamma}{delta}TCR signaling to elicit effector cytokine responses during neonatal sepsis, with IL-17 production during E. coli infection being driven by {gamma}{delta}TCR signaling, and IFN-{gamma} production during GBS infection occurring independently of {gamma}{delta}TCR signaling. Furthermore, we report that the divergent effector responses of {gamma}{delta} T cells during GBS and E. coli infections impart distinctive neuroinflammatory phenotypes on the neonatal brain. The present study reveals that the neonatal adaptive immune system differentially responds to distinct bacterial stimuli, resulting in unique neuroinflammatory phenotypes.

immunology↗