Ramirez Reyes Bryan, Madden Shelby, Meyer Kimberly A, Bartsch Brenden, Wright Austin P, Constant David A, Nice Timothy J
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA.
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA.
Cell Rep. 2025 Feb 25;44(2):115243. doi: 10.1016/j.celrep.2025.115243. Epub 2025 Feb 1.
Cell-intrinsic antiviral gene expression by intestinal epithelial cells (IECs) limits infection by enteric viral pathogens. Here, we find that neonatal IECs express antiviral genes at homeostasis that depend on interferon lambda (IFN-λ) and are required for early control of mouse rotavirus (mRV) infection. Neonatal homeostatic IFN-λ responses are independent of microbiota and pervasively distributed among IECs, distinguishing them from the homeostatic responses of adult mice. Developmental differences in homeostatic IFN-stimulated gene signatures of the intestine are regulated by maturation during the suckling-to-weanling transition, which includes reduced expression of Prdm1 by mature IECs. These studies identify developmental regulation of the homeostatic IFN-λ response, which is present in the neonatal intestine from birth, stimulated independent of microbiota, and preemptively protects IECs from viral infection. This intrinsically programmed antiviral response in early life is particularly important due to the absence of a robust microbiota or protective immune memory at birth, when the risk of enteric infection is high.
肠道上皮细胞（IECs）的细胞内源性抗病毒基因表达限制了肠道病毒病原体的感染。在此，我们发现新生IECs在稳态下表达抗病毒基因，这些基因依赖于干扰素λ（IFN-λ），并且是早期控制小鼠轮状病毒（mRV）感染所必需的。新生稳态IFN-λ反应独立于微生物群，广泛分布于IECs中，这使其与成年小鼠的稳态反应有所不同。肠道稳态IFN刺激基因特征的发育差异在从哺乳到断奶的转变过程中受成熟过程调控，其中包括成熟IECs中Prdm1表达的降低。这些研究确定了稳态IFN-λ反应的发育调控，该反应从出生起就存在于新生肠道中，独立于微生物群被刺激，并能预先保护IECs免受病毒感染。由于出生时缺乏强大的微生物群或保护性免疫记忆，而此时肠道感染风险很高，因此生命早期这种内在编程的抗病毒反应尤为重要。
