Interleukin 1 participates in the development of anti-Listeria responses in normal and SCID mice.
Using T- and B-cell deficient C.B-17 mice with the scid mutation, we have previously documented the existence of a T-cell-independent but interferon gamma-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 gamma, 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 1 alpha and interleukin 1 beta, we document that interleukin 1 participates neither directly in the induction of interferon gamma 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 1 alpha, anti-interleukin 1 beta, 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 gamma.
Rogers
H W
HW
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Sheehan
K C
KC
Brunt
L M
LM
Dower
S K
SK
Unanue
E R
ER
Schreiber
R D
RD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology / Q000502:physiology; D017472:Receptors, Interleukin-1
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D007371:Interferon-gamma