Involvement of Toll-Like Receptor 4 in Innate Immunity to Respiratory Syncytial Virus

TLDR

Toll‑like receptor 4 (TLR4) is a key component of innate immunity to gram‑negative bacterial infection, yet its antiviral role remains largely unexplored. The study aimed to determine whether TLR4 contributes to innate immunity against respiratory syncytial virus (RSV) and influenza virus. To test this, the authors compared immune responses in TLR4‑deficient (C57BL/10ScNCr) and TLR4‑expressing (C57BL/10Sn) mice following RSV and influenza infection. TLR4‑deficient mice displayed impaired NK cell and CD14⁺ cell pulmonary trafficking, reduced NK cell function, lower IL‑12 expression, and delayed virus clearance after RSV infection, but not after influenza, underscoring TLR4’s critical role in RSV innate immunity.

Abstract

ABSTRACT The mammalian Toll-like receptor 4, TLR4, is an important component in the innate immune response to gram-negative bacterial infection. The role of TLR4 in antiviral immunity has been largely unexplored. In this study, the in vivo immune responses to respiratory syncytial virus (RSV) and influenza virus infection were examined in TLR4-deficient (C57BL/10ScNCr) and TLR4-expressing (C57BL/10Sn) mice. TLR4-deficient mice challenged with RSV, but not influenza virus, exhibited impaired natural killer (NK) cell and CD14 + cell pulmonary trafficking, deficient NK cell function, impaired interleukin-12 expression, and impaired virus clearance compared to mice expressing TLR4. These findings suggest that Toll signaling pathways have an important role in innate immunity to RSV.