Exacerbation of acute and chronic murine tuberculosis by administration of a tumor necrosis factor receptor-expressing adenovirus.
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.
Gillis W. Long Hansen's Disease Center, Louisiana State University, Baton Rouge 70894.
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LB
Adams
C M
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Mason
J K
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Kolls
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Scollard
J L
JL
Krahenbuhl
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Nelson
D000208:Acute Disease; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002908:Chronic Disease; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000254:growth & development* / Q000302:isolation & purification; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology
D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins