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

Introduction:
Respiratory syncytial virus (RSV) infection of the upper respiratory tract facilitates both disease progression and transmission, with excessive inflammation contributing to more severe involvement of the lower airways. This study explores the immunomodulatory effects of Lactobacillus rhamnosus D3189 on viral dynamics and innate immune responses in well-differentiated nasal epithelial cells (WD-NECs).
Methods:
WD-NECs derived from healthy adult donors (N = 8) were cultured in vitro, pre-treated with L. rhamnosus D3189, and subsequently infected with RSV (strain RS4) after 24 hours. Viral replication and shedding were quantified using RT-qPCR and plaque assays. Cytotoxicity and epithelial barrier function were assessed via lactate dehydrogenase (LDH) release and ODN 1826 sodium transepithelial electrical resistance (TEER), respectively. Inflammatory and antiviral responses were measured using multiplex immunoassays, AlphaLISA, and ELISA.
Results:
RSV infection led to high levels of viral replication and shedding, compromised epithelial barrier function, and elicited strong pro-inflammatory cytokine and type I/III interferon responses. Treatment with L. rhamnosus D3189 alone did not induce cytotoxicity or inflammation. Although it did not affect viral replication, TEER, LDH release, or IFN-λ1/3 levels, D3189 significantly increased IFN-β production, decreased viral shedding, and suppressed RSV-induced cytokine and chemokine release.
Discussion:
L. rhamnosus D3189 modulates the epithelial immune response to RSV infection by enhancing antiviral signaling and dampening inflammation, without compromising epithelial integrity. These findings highlight its potential as a therapeutic approach to reduce RSV-related disease burden and transmission.