IFN-alpha beta-dependent, IFN-gamma secretion by bone-marrow-derived macrophages controls an intracellular bacterial infection

Several reports have indicated that cell lineages apart from NK and T cells can also express IFN-gamma. However, the biological relevance of this find ing is uncertain. We show in this study that bone marrow-derived macrophage s (BMMs) express IFN-gamma at the mRNA and protein level early after infect ion with Chlamydia pneumoniae. Increased IFN-gamma mRNA accumulation by inf ected BMMs is early, transient, and requires both bacterial and host protei n synthesis. The induction of IFN-gamma mRNA levels is independent of IL-12 and was dramatically enhanced in IL-10(-/-) BMMs. Such IL-10(-/-) BNMs con tained less bacteria than the wild-type controls, whereas IFN-gammaR(-/-) B MMs showed increased C. pneumoniae load. Inducible NO synthase (iNOS) also participates in the control of bacterial load, as shown by the enhanced num bers of C pneumoniae in iNOS(-/-) BMMs. However, the increased accumulation of iNOS mRNA and NO in C pneumoniae-infected BMMs depended on the presence of IFN-alpha beta, but was independent of IFN-gamma. Interestingly, IFN-al pha beta are also required for increased IFN-gamma mRNA accumulation in C p neumoniae-infected BMMs. Accordingly, IFN-alpha beta (-/-) BMMs showed high er levels of C pneumoniae than wild-type BMMs. Our findings unravel an auto crine/paracrine macrophage activation pathway by showing an IFN-alpha beta -dependent IFN-gamma and iNOS induction in response to infection, which pro tects macrophages against intracellular bacterial growth.