title: Deletion of TLR3 alters the pulmonary immune environment and mucus production during respiratory syncytial virus infection.
abstract: The detection of a viral infection by pattern recognition receptors (PAMPs) is an integral part of antiviral immunity. In these studies we have investigated the role of TLR3, which recognizes dsRNA, in Respiratory Syncytial virus (RSV) infection using B6 background mice with a TLR3 deletion. Although we observed no changes in viral growth, we did find that TLR3-/- mice demonstrated significant increases in mucus production in the airways of RSV-infected mice. The qualitative assessment was observed by examining differentially stained lungs, followed by immunohistochemical staining for gob5, a mucus-associated protein. The histopathologic observations were verified using quantitative gene expression analyses examining gob5 gene expression. Changes in pulmonary mucus production were accompanied by an increase in pulmonary IL-13 as well as IL-5 expression and eosinophils in the airways of TLR3-/- mice. Examining leukocytes in the airway indicated an accumulation of eosinophils in TLR3-/- mice, but not wild-type mice, after RSV infection. Isolated lung draining lymph node cells from TLR3-/- mice produced significant increases in Th2-type cytokines, IL-5, and IL-13, compared with wild-type TLR3+/+ mice only after RSV infection. To demonstrate a causative link, we depleted TLR3-/- mice of IL-13 during RSV infection and found that mucus and gob5 expression in the lungs was attenuated. Together, these studies highlight that although TLR3 may not be required for viral clearance, it is necessary to maintain the proper immune environment in the lung to avoid developing pathologic symptoms of disease.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Rudd
authors.forename: Jetse J
authors.initials: JJ
authors.lastname: Smit
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Lena
authors.initials: L
authors.lastname: Alexopoulou
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Schaller
authors.forename: Achim
authors.initials: A
authors.lastname: Gruber
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Berlin
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002460:Cell Line; D018118:Chloride Channels / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D018793:Interleukin-13 / Q000172:deficiency / Q000235:genetics; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009088:Mucoproteins / Q000096:biosynthesis / Q000235:genetics; D009093:Mucus / Q000276:immunology / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D051196:Toll-Like Receptor 3 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology
chemical_list: D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D016207:Cytokines; D018793:Interleukin-13; D009088:Mucoproteins; D051196:Toll-Like Receptor 3