D3189调节原代鼻上皮细胞中的抗病毒和炎症反应，减少呼吸道合胞病毒的脱落。

D3189 modulates antiviral and inflammatory responses in primary nasal epithelial cells, reducing respiratory syncytial virus shedding.

作者信息

Yarlagadda Tejasri, Stedman Jacob, Maresco-Pennisi Diane, Coleman Andrea, Cervin Anders, Spann Kirsten

机构信息

Centre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.

The Ear, Nose and Throat (ENT) Research Group, Centre for Clinical Research, Faculty of Health, Medicine and Behavioral Sciences, The University of Queensland, Brisbane, QLD, Australia.

出版信息

Front Cell Infect Microbiol. 2025 Jul 8;15:1625517. doi: 10.3389/fcimb.2025.1625517. eCollection 2025.

DOI:10.3389/fcimb.2025.1625517

PMID:40697815

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12279880/

Abstract

INTRODUCTION

Respiratory syncytial virus (RSV) infection in the upper respiratory tract promotes disease progression and transmission, with excessive inflammation contributing to severe lower respiratory tract involvement. This study investigates the immunomodulatory effects of D3189 on viral kinetics and innate immune responses in well-differentiated nasal epithelial cells (WD-NECs).

METHODS

WD-NECs from healthy adult donors (N = 8) were cultured , treated with D3189, and then infected with RSV (strain RS4) 24 hours later. Viral replication and shedding were assessed via RT-qPCR and plaque assays. Cytotoxicity and epithelial integrity were evaluated using LDH release and transepithelial electrical resistance (TEER). Inflammatory and antiviral responses were investigated using multiplex immunoassays, AlphaLISA, and ELISA.

RESULTS

RSV infection induced robust viral replication and shedding, disrupted epithelial barrier integrity, and triggered the release of pro-inflammatory cytokines and type I/III interferons. D3189 alone did not induce cytotoxicity or inflammation. While it had no effect on viral replication, TEER, LDH release, or IFN-λ1/3 levels, D3189 significantly enhanced IFN-β production, reduced viral shedding, and attenuated RSV-induced cytokine and chemokine responses.

DISCUSSION

D3189 modulates the epithelial immune response to RSV, reducing inflammation and viral shedding without compromising epithelial integrity. These findings support its potential as a novel strategy to limit RSV-associated infection and transmission.

摘要

引言

上呼吸道的呼吸道合胞病毒（RSV）感染会促进疾病进展和传播，过度炎症会导致严重的下呼吸道受累。本研究调查了D3189对分化良好的鼻上皮细胞（WD-NECs）中病毒动力学和先天免疫反应的免疫调节作用。

方法

培养来自健康成年供体（N = 8）的WD-NECs，用D3189处理，然后在24小时后用RSV（RS4株）感染。通过RT-qPCR和噬斑测定评估病毒复制和脱落。使用乳酸脱氢酶（LDH）释放和跨上皮电阻（TEER）评估细胞毒性和上皮完整性。使用多重免疫测定、AlphaLISA和酶联免疫吸附测定（ELISA）研究炎症和抗病毒反应。

结果

RSV感染诱导了强烈的病毒复制和脱落，破坏了上皮屏障完整性，并触发了促炎细胞因子和I/III型干扰素的释放。单独使用D3189不会诱导细胞毒性或炎症。虽然它对病毒复制、TEER、LDH释放或IFN-λ1/3水平没有影响，但D3189显著增强了IFN-β的产生，减少了病毒脱落，并减弱了RSV诱导的细胞因子和趋化因子反应。