The role of Toll-like receptor 4 versus interleukin-12 in immunity to respiratory syncytial virus.
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.
Ehl
Stephan
S
Children's Hospital, University of Freiburg, Freiburg, Germany. ehl@kikli.ukl.uni-freiburg.de
Bischoff
Ruth
R
Ostler
Tobias
T
Vallbracht
Simone
S
Schulte-Mönting
Jürgen
J
Poltorak
Alexander
A
Freudenberg
Marina
M
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009154:Mutation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D018664:Interleukin-12