Involvement of Beta Interferon in Enhancing Inducible Nitric Oxide Synthase Production and Antimicrobial Activity of Burkholderia pseudomallei- Infected Macrophages

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Abstract
Burkholderia pseudomallei is the causative agent of melioidosis, a life-threatening disease that affects both humans and animals. This bacterium is able to survive and multiply inside both phagocytic and nonphagocytic cells. We recently reported that mouse macrophages infected with B . pseudomallei fail to produce a significant level of inducible nitric oxide synthase (iNOS), a crucial enzyme needed for the cells to control the intracellular growth of this bacterium. In the present study, we extended our investigation to demonstrate that, unlike other gram-negative bacteria that have been investigated, B . pseudomallei only minimally activates beta interferon (IFN-β) production; this minimal activation leads to a low level of interferon regulating factor 1 (IRF-1) in the macrophages, in parallel with poor iNOS expression. Adding exogenous IFN-β to the system could upregulate IRF-1 production, which in turn could enhance iNOS expression in the B . pseudomallei -infected macrophages and lead to suppression of the intracellular growth of this bacterium. Taken together, these results imply that the failure of macrophages to successfully control the growth and survival of intracellular B . pseudomallei is related, at least in part, to the defective production of IFN-β, which modulates the ability of macrophages to synthesize iNOS.