Endogenous IL-1 is required for neutrophil recruitment and macrophage activation during murine listeriosis.
By using a mixture of neutralizing mAbs to IL-1 alpha, IL-1 beta, and to the type I IL-1R, we previously documented a regulatory role for IL-1 in the development of anti-Listeria responses in mice. Both normal C.B-17 and severe combined immunodeficiency (SCID) mice injected with this mixture of Abs exhibit decreased resistance to Listeria. In this study, we demonstrate that the neutralization of IL-1 activity in SCID mice results in a major defect in neutrophil migration to the peritoneum, in response to Listeria infection. Moreover, anti-IL-1 treatment also inhibits Listeria-induced peripheral blood leukocytosis at all time points examined. We also show that mice injected with anti-IL-1 Abs failed to elaborate class II MHC-positive peritoneal macrophages in vivo at any time during Listeria infection. Even though peritoneal macrophages from anti-IL-1-treated Listeria-infected mice are not activated to express MHC class II molecules, IFN-gamma production in vivo is normal. Moreover, the macrophages are unresponsive to IFN-gamma in vitro, as assayed by MHC class II expression, even when rIL-1 is added. rIL-1 also is unable to increase the expression of IFN-gamma-induced surface class II MHC molecules on resident peritoneal macrophages in vitro. These results indicate that endogenously produced IL-1 plays an important role in Listeria-dependent neutrophil migration, increase in blood leukocyte number, generation of MHC class II-positive macrophages in vivo, and macrophage responsiveness to IFN-gamma.
Rogers
H W
HW
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Tripp
C S
CS
Schreiber
R D
RD
Unanue
E R
ER
D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009504:Neutrophils / Q000276:immunology*; D011994:Recombinant Proteins; D013154:Spleen / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D011994:Recombinant Proteins; D007371:Interferon-gamma