Reduced PICD in monocytes mounts altered neonate immune response to Candida albicans

Background: Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO). Hypothesis: Phagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulation of TLR-mediated immune responses. Methods: The ability to phagocytose C. albicans, expression of TLRs, the induction of apoptosis (assessment of sub-G1 and nick-strand breaks) were analyzed by FACS. TLR signalling was induced by agonists such as lipopolysaccharide (LPS), Pam3Cys, FSL-1 and Zymosan and blocked (neutralizing TLR2 antibodies and MYD88 inhibitor). Results: Phagocytic indices of PBMO and CBMO were similar. Following stimulation with agonists and C. albicans induced up-regulation of...

背景：白色念珠菌（Candida albicans, C. albicans）所致侵袭性真菌感染在极低出生体重（extremely low birthweight, ELBW）婴儿中频发，且预后不良。白色念珠菌吞噬作用可启动单核细胞凋亡（吞噬诱导细胞死亡，phagocytosis induced cell death, PICD）。新生儿脐带血单核细胞（neonatal cord blood monocytes, CBMO）的PICD水平降低。
假设：白色念珠菌吞噬诱导的PICD在新生儿单核细胞（CBMO）与成人外周血单核细胞（adult peripheral blood monocytes, PBMO）间存在差异，其原因在于toll样受体（Toll-like receptor, TLR）介导的免疫应答刺激水平较低。
方法：采用流式细胞术（FACS）分析单核细胞的白色念珠菌吞噬能力、TLR表达水平及凋亡诱导情况（通过sub-G1期检测和缺口链断裂评估）。利用脂多糖（lipopolysaccharide, LPS）、Pam3Cys、FSL-1及Zymosan等激动剂诱导TLR信号通路，并通过中和性TLR2抗体及MYD88抑制剂阻断该通路。
结果：PBMO与CBMO的吞噬指数相近。经激动剂刺激及白色念珠菌诱导后，...