Salmonella infection accelerates potential maturation of the intestinal epithelium

Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Salmonella Typhimurium results in a Myd88-dependent accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. To study intestinal epithelial maturation during homeostatic conditions, we isolated intestinal epithelial cells from small intestinal tissue obtained from C57Bl/6J wild type specific pathogen free (SPF) newborn (5-day-old) and adult (8-week-old) mice, C57Bl/6J Myd88-/- newborn (5-day-old) mice and C57Bl/6N wild tyoe germ free (GF) and SPF newborn (5-day-old) mice. In addition, we isolated intestinal epithelial cells from newborn (5-day-old) and adult (8-week-old) mice that had been infected 4 days earlier with Salmonella Typhimurium. We then isolated RNA and performed 3'mRNA-Seq. Four biological replicates were used per group.

肠道代谢、宿主-微生物与免疫稳态的产后建立，是时序精准且调控严谨的发育与适应过程的共同结果。本研究发现，侵袭性肠道致病菌鼠伤寒沙门氏菌（Salmonella Typhimurium）的感染，可通过依赖髓系分化因子88（Myd88）的通路加速新生小鼠上皮细胞的成熟，并使成年肠道组织所特有的抗菌、代谢、发育及再生特征提前出现。为探究稳态条件下的肠道上皮成熟过程，本研究从以下小鼠的小肠组织中分离肠道上皮细胞：C57Bl/6J野生型无特定病原体（SPF）新生（5日龄）及成年（8周龄）小鼠、C57Bl/6J Myd88基因敲除（Myd88-/-）新生（5日龄）小鼠，以及C57Bl/6N野生型无菌（GF）和无特定病原体（SPF）新生（5日龄）小鼠。此外，本研究还从感染鼠伤寒沙门氏菌4天后的新生（5日龄）及成年（8周龄）小鼠中分离肠道上皮细胞。随后我们提取RNA并进行3'端mRNA测序（3'mRNA-Seq），每组设置4个生物学重复。