IMMUNE-COMPLEXES INHIBIT ANTIMICROBIAL RESPONSES THROUGH INTERLEUKIN-10 PRODUCTION - EFFECTS IN SEVERE COMBINED IMMUNODEFICIENT MICE DURINGLISTERIA INFECTION

The presence of soluble antigen-antibody complexes renders mice highly susceptible to infection with the intracellular pathogen Listeria mon ocytogenes, In this report we show that this inhibition is manifest at the level of the innate immune response and is mediated by IL-10. Lik e immunocompetent mice, mice with the severe combined immunodeficient mutation (SCID) injected with immune complexes died from a sublethal d ose of L. monocytogenes. These mice were protected if pretreated with neutralizing antibodies to IL-10. In vitro, immune complexes stimulate d IL-10 production by SCID splenocytes and splenic macrophages. Likewi se, immune complexes inhibited TNF and IFN-gamma production by SCID sp lenocytes cultured with heat-killed-L. monocytogenes, This inhibition was reversed by neutralization of IL-10 but not IL-4 or TGF-beta. Immu ne complexes and rIL-10 inhibited cytokine production by SCID splenocy tes if added before or simultaneously with heat-killed-L. monocytogene s, These data support a model in which immune complexes modulate host defense and the immune response by stimulating the production of IL-10 from macrophages.