Early activation of splenic macrophages by tumor necrosis factor alpha is important in determining the outcome of experimental histoplasmosis in mice.
Experimental infection of animals with Histoplasma capsulatum caused a massive macrophage infiltration into the spleen and induced the production of tumor necrosis factor alpha (TNF-alpha) locally. The cytokine was also produced in vitro by peritoneal exudate macrophages exposed to a large inoculum of yeast cells. Depletion of the cytokine by injection of polyclonal sheep anti-TNF-alpha antibody was detrimental to sublethally infected mice. Fungous burdens in the spleens of TNF-alpha-depleted mice were higher than they were in the infected control mice at days 2, 7, and 9 after infection, and the antibody-treated animals succumbed to the infection. Histopathological study of spleen sections revealed that splenic macrophages were not able to control proliferation of intracellular yeasts as a result of TNF-alpha depletion. It seems that TNF-alpha plays a role in early activation of splenic macrophages which is important in controlling the outcome of an infection.
Wu-Hsieh
B A
BA
Department of Microbiology and Immunology, UCLA School of Medicine 90024.
Lee
G S
GS
Franco
M
M
Hofman
F M
FM
D000818:Animals; D006660:Histoplasmosis / Q000276:immunology* / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha