How the host defenses control rickettsiae in the cytosol of nonphagocytic host cells, where they are not exposed to antibodies or phagocytes, has posed a difficult question. Rickettsia conorii infection of a mouse fibroblast cell line was inhibited in a dose-dependent manner by nitrogen oxide synthesized by eukaryotic host cells stimulated by interferon-γ or tumor necrosis factor-α. L-arginine was the source of the nitric oxide as demonstrated by competitive inhibition by N(G)-monomethyl-L-arginine. Nitric oxide synthesis required host cell protein synthesis and had an approximately 48-hour lag phase following cytokine stimulation. At low doses of interferon-γ and tumor necrosis factor-α, which had no detectable response as single agents, dramatic synergistic nitric oxide synthesis and antirickettsial effects were observed.
|Original language||English (US)|
|Number of pages||8|
|Journal||American Journal of Pathology|
|State||Published - Dec 1 1993|
ASJC Scopus subject areas
- Pathology and Forensic Medicine