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

母乳中的骨髓源性抑制细胞（MDSC）对新生儿免疫发育的作用

• 批准号: 431535861
• 负责人: Dr. Natascha Köstlin-Gille
• 金额: --
• 依托单位: Abteilung IV: Neonatologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/431535861?language=en
• 关键词: role; myeloid; derived; suppressor; cells

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.

感染是早产儿治疗中最重要的并发症之一，通常会导致死亡或长期后果。与成人相比，新生儿对感染的易感性增加归因于免疫反应的改变。大多数新生儿感染涉及粘膜表面，突出了粘膜免疫的特定缺陷。在怀孕期间，胎儿在基本无菌的环境中发育，受到母体免疫力的保护免受病原体的侵害。出生后，新生儿逐渐被微生物定植，直接将新生儿免疫系统暴露于潜在的病原体。在这一过渡时期，新生儿对感染的抵抗力很强。同时，微生物组建立的主要阶段发生，并且认为需要导致感染的脆弱性的相同机制来允许不受干扰的微生物组建立。母乳（BM）是婴儿的完美营养。除了所有必需的营养成分外，BM还含有非营养免疫因子和免疫细胞，可以促进微生物组的建立，保护新生儿免受急性感染，并预防晚年的慢性炎症性疾病，如肥胖和过敏。最近，我们的研究小组发现母乳中含有大量的髓源性抑制细胞（MDSC），这是一种抑制或调节其他免疫细胞的髓细胞。本研究拟通过转录组和微生物组分析、临床研究和小鼠体内模型等描述性方法，探讨BM-MDSC从母体到儿童的转移可能影响粘膜免疫和微生物组的建立，从而调节免疫系统发育、新生儿急性炎症和以后的慢性炎症。不同的小鼠模型将作为免疫成熟、新生儿期急性炎症性疾病和晚年慢性炎症性疾病的例子。该研究可能为母乳的免疫调节特性提供新的见解。根据研究结果，可能会开发新的预防和治疗方法来治疗新生儿和早产儿，以改善这些患者的结局。