Tumor necrosis factor-α is required in the protective immune response against mycobacterium tuberculosis in mice

TLDR

The immunological mechanisms underlying protection and pathogenesis in tuberculosis remain poorly understood. The study examined how tumor necrosis factor‑α contributes to tuberculosis by inhibiting its action in mouse models. TNF‑α was neutralized with a monoclonal antibody and a TNF receptor‑deficient mouse strain was used. Both models showed that TNF‑α and its 55‑kDa receptor are essential for protection and early macrophage reactive‑nitrogen production, and that granuloma numbers were unchanged but necrosis occurred only in TNF‑α or receptor‑deficient mice, indicating that TNF‑α is required for protection but not the sole cause of tissue damage.

Abstract

Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined the extent to which tumor necrosis factor-alpha (TNF alpha) contributes to this disease using murine models in which the action of TNF alpha is inhibited. TNF alpha was neutralized in vivo by monoclonal antibody; in addition, a mouse strain with a disruption in the gene for the 55 kDa TNF receptor was used. The data from both models established that TNF alpha and the 55 kDa TNF receptor are essential for protection against tuberculosis in mice, and for reactive nitrogen production by macrophages early in infection. Granulomas were formed in equal numbers in control and experimental mice, but necrosis was observed only in mice deficient in TNF alpha or TNF receptor. TNF alpha and the 55 kDa TNF receptor are necessary conditions for protection against murine M. tuberculosis infection, but are not solely responsible for the tissue damage observed.