Fighting infant infections with myeloid-derived suppressor cells

Area of Science:

• Immunology
• Neonatal Research
• Molecular Biology

Background:

• Myeloid-derived suppressor cells (MDSCs) are implicated in newborn antimicrobial responses.
• The specific signals initiating MDSC differentiation in neonates were previously unidentified.

Purpose of the Study:

• To elucidate the molecular mechanisms by which lactoferrin (LF) induces MDSC differentiation in newborns.
• To evaluate the therapeutic potential of LF-generated MDSCs in a neonatal disease model.

Main Methods:

• Investigated the conversion of newborn neutrophils and monocytes to MDSCs using lactoferrin (LF).
• Utilized the low-density lipoprotein receptor-related protein-2 (LRP2) receptor and NF-κB signaling pathway.
• Assessed the efficacy of adoptive transfer of LF-induced MDSCs in a murine model of necrotizing enterocolitis.

Main Results:

• Lactoferrin (LF) was shown to induce the differentiation of newborn neutrophils and monocytes into functional MDSCs.
• This conversion process involves the LRP2 receptor and activation of the NF-κB pathway.
• Adoptive transfer of LF-generated MDSCs significantly improved survival rates in newborn mice with necrotizing enterocolitis.

Conclusions:

• Lactoferrin (LF) plays a crucial role in generating antimicrobial MDSCs from neonatal immune cells.
• MDSCs exhibit a protective function in newborns, contrary to some previous assumptions.
• MDSC therapy holds promise for treating inflammatory conditions in preterm infants, such as necrotizing enterocolitis.