Exacerbation of acute and chronic murine tuberculosis by administration of a tumor necrosis factor receptor-expressing adenovirus.

Abstract

Tumor necrosis factor (TNF) plays a pivotal role in inflammatory phenomena that culminate in either pathogenesis or resistance in mycobacterial disease. The regulatory role of TNF in murine tuberculosis was examined by administering a recombinant adenovirus encoding a fusion protein consisting of the human 55-kDa TNF receptor extracellular domain and the mouse IgG heavy chain domain (AdTNFR). During acute infections with Mycobacterium tuberculosis, AdTNFR pretreatment induced elevated mycobacterial burdens of 1 log10 in the tissues of H37Ra-infected mice and 2 log10 (spleen and liver) and 4 log10 (lungs) in H37Rv-infected mice. In mice infected chronically with H37Rv, AdTNFR treatment induced a 3-log10 increase of M. tuberculosis in the lungs, in which a tuberculous bronchopneumonia developed with numerous acid-fast bacilli visible in alveoli and bronchi. Administration of AdTNFR may serve as a useful model for studying the pathogenesis and chemotherapy of progressive primary tuberculosis.