IFN-αβ-Dependent, IFN-γ Secretion by Bone Marrow-Derived Macrophages Controls an Intracellular Bacterial Infection

Abstract

Several reports have indicated that cell lineages apart from NK and T cells can also express IFN-γ. However, the biological relevance of this finding is uncertain. We show in this study that bone marrow-derived macrophages (BMMs) express IFN-γ at the mRNA and protein level early after infection with Chlamydia pneumoniae. Increased IFN-γ mRNA accumulation by infected BMMs is early, transient, and requires both bacterial and host protein synthesis. The induction of IFN-γ mRNA levels is independent of IL-12 and was dramatically enhanced in IL-10−/− BMMs. Such IL-10−/− BMMs contained less bacteria than the wild-type controls, whereas IFN-γR−/− BMMs showed increased C. pneumoniae load. Inducible NO synthase (iNOS) also participates in the control of bacterial load, as shown by the enhanced numbers 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-αβ, but was independent of IFN-γ. Interestingly, IFN-αβ are also required for increased IFN-γ mRNA accumulation in C. pneumoniae-infected BMMs. Accordingly, IFN-αβR−/− BMMs showed higher levels of C. pneumoniae than wild-type BMMs. Our findings unravel an autocrine/paracrine macrophage activation pathway by showing an IFN-αβ-dependent IFN-γ and iNOS induction in response to infection, which protects macrophages against intracellular bacterial growth.