Surface interleukin-10 inhibits listericidal activity by primary macrophages.
Interleukin-10 (IL-10) down-regulates multiple functions of monocytes and macrophages, including the ability of macrophages to kill many intracellular microorganisms. The experiments presented here test the hypothesis that IL-10 expressed on the cell surface inhibits the ability of primary mouse macrophages to kill the facultative, intracellular bacterium Listeria monocytogenes. We show that, in contrast to macrophages from normal mice, both bone marrow-derived macrophages (BMDM) and thioglycollate-elicited macrophages obtained from IL-10-/- mice can kill L. monocytogenes. Treatment with anti-IL-10 monoclonal antibody (mAb) enables BMDM from normal mice and thioglycollate-elicited macrophages from RAG-2-/- mice (which lack T or B cell-derived IL-10) to kill L. monocytogenes, and concurrently down-regulates the expression of surface IL-10. Surface IL-10 on paraformaldehyde-fixed cells can inhibit nitric oxide (NO) production by interferon-gamma (IFN-gamma)-stimulated macrophages from IL-10-/- mice, thus directly showing functional activity of surface IL-10. Taken together, these studies indicate that macrophage surface IL-10 is biologically active and down-regulates macrophage bactericidal activity.
Fleming
S D
SD
Department of Medicine, National Jewish Medical and Research Center, University of Colorado Health Science Center, Denver, USA.
Leenen
P J
PJ
Freed
J H
JH
Campbell
P A
PA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D013864:Thioglycolates / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D013864:Thioglycolates; C064655:V(D)J recombination activating protein 2; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma