Using T- and B-cell deficient C.B-17 mice with the scid3 mutation, we have previously documented the existence of a T-cell-independent but interferon γ-dependent pathway of macrophage activation that confers upon the host partial resistance to the facultative intracellular bacterium Listeria monocytogenes. This pathway is operative in both normal and SCID mice and consists of at least four components: interferon γ, tumor necrosis factor, macrophages, and natural killer cells. Here we demonstrate that interleukin 1 also participates in this pathway but at a different site of action. Using monoclonal antibodies that neutralize the biologic activities of interleukin 1α and interleukin 1β, we document that interleukin γ participates neither directly in the induction of interferon γ from isolated SCID natural killer cells nor in the antigen-specific activation of CD4+ T cells derived from Listeria-immune C.B-17 mice. In contrast, injection of a mixture of anti-interleukin 1α, anti-interleukin 1β, and a newly derived monoclonal antibody specific for the murine type I interleukin-1 receptor into either SCID or normal C.B-17 mice blocked the in vivo elaboration of class II major histocompatibility complex-positive macrophages after infection of the animals with Listeria. Moreover, SCID mice treated with the anti-interleukin-1 mixture failed to control the growth of Listeria in vivo and eventually succumbed to the infection. These results document that endogenously produced interleukin 1 plays an obligate role in the Listeria-dependent induction of activated macrophages in vivo and demonstrate that the action of interleukin 1 is distinct from the generation of natural killer cell-derived interferon γ.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Feb 1 1992|
- Microbial infection
- Monoclonal antibody
- Natural immunity