TGF-beta Prevents Eosinophilic Lung Disease but Impairs Pathogen Clearance

Microbes Infect. 2005 Mar;7(3):365-74. doi: 10.1016/j.micinf.2004.11.012. Epub 2005 Feb 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cryptococcosis / drug therapy
  • Cryptococcosis / immunology
  • Female
  • Gene Expression
  • Inflammation / drug therapy
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • 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

Substances

  • Transforming Growth Factor beta