Effect of IFN-gamma and endogenous TNF on the histopathological changes in the liver of Listeria monocytogenes-infected mice.
During primary infection of mice with Listeria monocytogenes, the bacteria proliferate extensively in the liver resulting in the development of inflammatory lesions in this organ. In the present study, the effect of interferon-gamma (IFN-gamma) on the development of these lesions, and the involvement of endogenous tumour necrosis factor-alpha (TNF-alpha) in the IFN-gamma-induced effects were evaluated. During an infection of naive mice with L. monocytogenes, two types of inflammatory lesions in the liver could be distinguished: large necrotic lesions consisting of granulocytes and/or exudate macrophages and small lesions containing mainly mature macrophages, i.e. BM8-expressing cells. Necrotic lesions were characterized by the presence of CD11b-expressing cells and consisted mainly of granulocytes during days 1 and 2 of infection and thereafter of exudate macrophages. The lesions consisting of mature macrophages and lymphocytes were not associated with necrosis and were called granulomatous lesions. Some of the granulomatous lesions contained many cells that expressed Ia antigen, i.e. activated cells. Treatment of mice with recombinant (r)IFN-gamma before injection of L. monocytogenes resulted in a decrease in the number of necrotic lesions and an increase in the number of granulomatous lesions in the liver, which was accompanied by a reduced bacterial proliferation in the liver. The effect of rIFN-gamma on the development of the various types of inflammatory lesions in the liver during infection with L. monocytogenes was abrogated by anti-TNF-alpha antibody and this antibody abrogated the rIFN-gamma-induced reduction of bacterial proliferation in the liver as well. Together, the results demonstrate that endogenous TNF-alpha plays a key role in the effects of rIFN-gamma on the inflammatory response in the liver during an infection with L. monocytogenes.
Langermans
J A
JA
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Mayanski
D M
DM
Nibbering
P H
PH
van der Hulst
M E
ME
van de Gevel
J S
JS
van Furth
R
R
D000818:Animals; D005260:Female; D007371:Interferon-gamma / Q000627:therapeutic use*; D008089:Listeria monocytogenes / Q000254:growth & development; D008088:Listeriosis / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma