Details

Autor(en) / Beteiligte

• Briscoe, Helen
• Roach, Daniel R.
• Meadows, Natalie
• Rathjen, Deborah
• Britton, Warwick J.

Titel

A novel tumor necrosis factor (TNF) mimetic peptide prevents recrudescence of Mycobacterium bovis bacillus Calmette-Guerin (BCG) infection in CD4+ T cell-depleted mice

Ist Teil von

• Journal of leukocyte biology, 2000-10, Vol.68 (4), p.538-544

Ort / Verlag

United States: Society for Leukocyte Biology

Erscheinungsjahr

2000

Quelle

Wiley

Beschreibungen/Notizen

• Tumor necrosis factor (TNF) is required to control mycobacterial infections, but its therapeutic value is limited by its in vivo instability and toxicity. The efficacy of a nontoxic TNF‐mimetic peptide (TNF70–80) was tested in mice infected with Mycobacterium bovis bacillus Calmette‐Guerin (BCG).In vitro TNF70–80 and recombinant human TNF (hTNF) acted with interferon gamma (IFN‐γ) to reduce bacterial replication and to induce synthesis of bactericidal nitric oxide (NO) in BCG‐infected, bone marrow‐derived murine macrophages. The dose‐dependent inhibitory effect on bacterial replication was blocked by neutralizing anti‐IFN‐γ and anti‐hTNF mAbs. Further,n‐monomethyl‐l‐arginine (n‐MMA) and a soluble TNF‐receptor I (TNFRI‐IgG) blocked bacterial growth and NO synthesis. Therefore, the peptide acted with IFN‐γ via induction of NO synthase and signaled through TNFRI receptors. Concomitantin vivo treatment with TNF70–80 or hTNF prevented reactivation of chronic BCG infection in mice depleted of CD4+ T cells by injecting anti‐CD4 antibodies. Granuloma number and bacterial load were comparable in treated, T cell‐depleted mice and in chronically infected, intact animals. Thus, TNF70–80 and hTNF can modulate recrudescent BCG infection in CD4+ T cell‐deficient mice.