Growth inhibition of Mycobacterium bovis by IFN-gamma stimulated macrophages: regulation by endogenous tumor necrosis factor-alpha and by IL-10.
Murine bone marrow-derived macrophages (BMM) are able to inhibit the intracellular growth of Mycobacterium bovis and Mycobacterium tuberculosis H37Rv after activation with recombinant (r) IFN and growth inhibition is mediated by reactive nitrogen intermediates (RNI) derived from L-arginine. We now demonstrate that tumor necrosis factor (TNF)-alpha acts as an endogenous cofactor in the induction of mycobacterial growth inhibition. TNF-alpha was produced by BMM stimulated with rIFN-gamma and infected with mycobacteria, and a specific antiserum to TNF-alpha inhibited rIFN-gamma-induced production of RNI as well as growth inhibition of M. bovis. IL-10, a cytokine which suppresses antimycobacterial macrophage functions, was also produced by BMM activated with rIFN-gamma and infected with M. bovis. IFN-gamma-induced production of TNF-alpha and of reactive nitrogen intermediates as well as mycobacterial growth inhibition were inhibited by exogenous IL-10, but only when given prior to IFN-gamma stimulation. We conclude that the outcome of mycobacterial infection is regulated by a coordinate interplay between IFN-gamma, TNF-alpha and IL-10.
Flesch
I E
IE
Department of Immunology, University of Ulm, Germany.
Hess
J H
JH
Oswald
I P
IP
Kaufmann
S H
SH
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000254:growth & development / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000199:Actins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma