TGF-β prevents eosinophilic lung disease but impairs pathogen clearance

• Published in: Microbes and infection 2005-03, Vol.7 (3), p.365-374
• Main Authors: Williams, Andrew Evan, Humphreys, Ian Robert, Cornere, Megan, Edwards, Lorna, Rae, Aaron, Hussell, Tracy
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cryptococcosis - drug therapy; Cryptococcosis - immunology; Cytokines; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Inflammation; Inflammation - drug therapy; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbiology; Mouse; Orthomyxoviridae Infections - drug therapy; Orthomyxoviridae Infections - immunology; Plasmids; Pulmonary Eosinophilia - drug therapy; Pulmonary Eosinophilia - immunology; Pulmonary Eosinophilia - prevention & control; Respiratory Syncytial Virus Infections - drug therapy; Respiratory Syncytial Virus Infections - immunology; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - physiology; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - pharmacology; Transforming Growth Factor beta - physiology; Viral
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2004.11.012

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-β 1 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-β treatment could be used to prevent pulmonary, pathogen-driven eosinophilic disease, although anti-pathogen strategies will need to be administered concordantly.