title: TGF-beta prevents eosinophilic lung disease but impairs pathogen clearance.
abstract: Respiratory infections are the third leading cause of death worldwide. Complications arise directly as a consequence of pathogen replication or indirectly due to aberrant or excessive immune responses. In the following report, we evaluate the efficacy, in a murine model, of nasally delivered DNA encoding TGF-beta1 to suppress immunopathology in response to a variety of infectious agents. A single nasal administration suppressed lymphocyte responses to Cryptococcus neoformans, influenza virus and respiratory syncytial virus. The suppression did not depend on the phenotype of the responding T cell, since both Th1 and Th2 responses were affected. During Th2-inducing infection, pulmonary eosinophilic responses were significantly suppressed. In all cases, however, suppressed immunity correlated with increased susceptibility to infection. We conclude that nasal TGF-beta treatment could be used to prevent pulmonary, pathogen-driven eosinophilic disease, although anti-pathogen strategies will need to be administered concordantly.
authors.affiliation: Kennedy Institute of Rheumatology, Charing Cross Campus, Imperial College London, London W6 8LM, UK. a.williams@imperial.ac.uk
authors.forename: Andrew Evan
authors.initials: AE
authors.lastname: Williams
authors.forename: Ian Robert
authors.initials: IR
authors.lastname: Humphreys
authors.forename: Megan
authors.initials: M
authors.lastname: Cornere
authors.forename: Lorna
authors.initials: L
authors.lastname: Edwards
authors.forename: Aaron
authors.initials: A
authors.lastname: Rae
authors.forename: Tracy
authors.initials: T
authors.lastname: Hussell
mesh_terms: D000818:Animals; D003453:Cryptococcosis / Q000188:drug therapy / Q000276:immunology; D005260:Female; D015870:Gene Expression; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000276:immunology; D010957:Plasmids; D011657:Pulmonary Eosinophilia / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology
chemical_list: D016212:Transforming Growth Factor beta