Role of type I interferons during macrophage activation by lipopolysaccharide

Activation of macrophages by bacterial lipopolysaccharide (LPS) is accompanied by the secretion of type I interferons (IFNs) which can act in an autocrine manner, We examined the role of type I IFNs in macrophage responses to LPS using bone marrow-derived macrophages (BMM) from IFNAR1-/- mice, which lack a component of the type I IFN receptor and do not respond to type I IFNs, We found that, unlike wild-type (WT) BMM, LPS-treated IFNAR1-/- cells failed to produce nitric oxide (NO), or express inducible NO synthase (iNOS), indicating that type I IFNs are essential for all LPS-stimulated NO production in BMM, Exogenously added type II IFN (IFN gamma) rescued these responses in LPS-treated IFNAR1-/- BMM, In contrast to effects on NO, type I IFNs negatively regulated respiratory burst activity in LPS-primed BMM, We also found that while type I IFNs mediated the anti-proliferative effects of lower concentrations of LPS, at higher concentrations LPS acted in a type I IFNs-independent manner. Finally, we report that type I IFNs are a survival factor for BMM, Despite this, the ability of LPS to also prevent apoptosis in BMM was independent of type I IFNs, These findings highlight the diverse roles of type I IFNs in mediating LPS-stimulated macrophage responses. (C) 2000 Academic Press.