The role of toll‐like receptor 4 versus interleukin‐12 in immunity to respiratory syncytial virus

S Ehl, R Bischoff, T Ostler, S Vallbracht… - European journal of …, 2004 - Wiley Online Library
S Ehl, R Bischoff, T Ostler, S Vallbracht, J Schulte‐Mönting, A Poltorak, M Freudenberg
European journal of immunology, 2004Wiley Online Library
Toll‐like receptors (TLR) and IL‐12 represent key elements of innate immunity. Using
C57BL/10 ScCr mice it was shown that TLR4 is important for control of infection with
respiratory syncytial virus (RSV). Since these mice have an additional defect in the IL‐12R,
we reinvestigated immunity to RSV in several C57BL/10 and BALB/c mouse strains lacking
a functional TLR4, a functional IL‐12–IL‐12R interaction or both. In the absence of a
functional IL‐12 axis, early virus control was impaired in C57BL/10 mice, but not in BALB/c …
Abstract
Toll‐like receptors (TLR) and IL‐12 represent key elements of innate immunity. Using C57BL/10 ScCr mice it was shown that TLR4 is important for control of infection with respiratory syncytial virus (RSV). Since these mice have an additional defect in the IL‐12R, we reinvestigated immunity to RSV in several C57BL/10 and BALB/c mouse strains lacking a functional TLR4, a functional IL‐12–IL‐12R interaction or both. In the absence of a functional IL‐12 axis, early virus control was impaired in C57BL/10 mice, but not in BALB/c mice. By contrast, TLR4 had no impact on RSV elimination. Pulmonary NK cell recruitment was impaired in IL‐12 deficient BALB/c mice and NK cytotoxicity was reduced in IL‐12/IL‐12R‐deficient mice of both genetic backgrounds. Absence of TLR4 had no impact on NK cell recruitment or NK activity nor on recruitment of other pulmonary inflammatory cells. Activation of RSV‐specific T cell immunity, including T cell mediated immunopathology, was normal in all mutant strains. These findings clearly argue against a significant role for TLR4 and define a limited role for IL‐12 in primary murine RSV infection.
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