Splenic marginal metallophilic macrophages and marginal zone macrophages are the major interferon-alpha/beta producers in mice upon intravenous challenge with herpes simplex virus.

The interferon (IFN)-alpha/beta-producing cells (IPCs) are localized predominantly in the spleen, in particular in the marginal zones (MZ), in C57BL/6 mice injected intravenously (i.v.) with UV-inactivated herpes simplex virus (HSV). We defined the phenotype of these murine IPCs using simultaneous immunohistochemical labelling of intracellular IFN-alpha/beta and various surface antigens. We found that the IPCs in the MZ are not dendritic cells because they did not express major histocompatibility complex (MHC) class II and CD11c molecules. Furthermore, they did not express antigenic markers typical for T cells, B cells or red pulp macrophages. In contrast, the majority of IPCs were stained by the anti-sialoadhesin monoclonal antibody (MoAb) SER-4, which is specific for marginal metallophilic macrophages. In addition, a minor part of the IPCs with a more outward localization in the MZ were stained by a MoAb specific for MZ macrophages. We conclude that the massive IFN-alpha/beta production in the MZ of the spleen upon in vivo stimulation by HSV is mainly exerted by marginal metallophilic macrophages and to a lesser extent by MZ macrophages.