The role of myeloid derived suppressor cells (MDSC) from breast milk for immune development of the neonate

• Applicant: Dr. Natascha Köstlin-Gille
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 431535861

Infections are one of the most important complications in the treatment of preterm infants and often lead to dead or long-term consequences. The increased susceptibility to infections seen in neonates is attributed to an altered immune response compared to adult individuals. Most neonatal infections involve mucosal surfaces,highlighting specific defects in mucosal immunity. During pregnancy, the fetus develops in a largely sterile environment, protected from pathogens by maternal immunity. After birth, the newborn becomes progressively colonized with microbes, directly exposing the neonatal immune system to potential pathogens. During that transitional period, newborns are highly susceptive to infections. Simultaneously, the main phase of microbiome establishment takes place and it is supposed that the same mechanisms causing the vulnerability to infections otherwise are needed to allow undisturbed microbiome establishment.Breast milk (BM) is the perfect nutrition for infants. Besides all essential nutritional components, BM contains non-nutrient immunological factors and immune cells that may promote microbiome establishment and protect newborns against acute infections and prevents chronic inflammatory diseases in later life like obesity and allergies. Recently, our group showed that breast milk contains large numbers of myeloid derived suppressor cells (MDSC), which are myeloid cells that suppress or modulate other immune cells. In the planned project, we aim to investigate the hypotheses that the transfer of BM-MDSC from mother to child may influence mucosal immunity and microbiome establishment, thereby regulating immune system development, acute inflammation in neonates and chronic inflammation in later life.For this purpose, descriptive approaches like transcriptome and microbiome analyses, a clinical study and in vivo mouse models will be exploited. The different mouse models will serve as examples for immune maturation, acute inflammatory diseases during neonatal time and chronic inflammatory diseases in later life.The study may provide new insights in immunomodulatory properties of breast milk. Based on the results of the study, new prophylactic and therapeutic approaches in the treatment of newborn and preterm infants may be developed to improve the outcome of these patients.

• DFG Programme: Research Grants