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Vet Pathol 39:190-199 (2002)
© 2002 American College of Veterinary Pathologists

Inducible Nitric Oxide Synthase and Nitrotyrosine in Listeric Encephalitis: A Cross-species Study in Ruminants

H. Pfister, K. A. Remer, M. Brcic, R. Fatzer, S. Christen, S. Leib and T. W. Jungi

Institutes of Veterinary Virology (HP, KAR, MB, TWJ), Animal Neurology (RF), and Infectious Diseases (SC, SL), University of Berne, Berne, Switzerland

Listeria monocytogenes (LM) is a Gram-positive facultative intracellular bacterium that causes fatal meningoencephalitis in humans and ruminants. A current paradigm predicts that intracellular bacteria are controlled by nitric oxide (NO) whose synthesis is catalyzed by inducible nitric oxide synthase (iNOS). The ability of macrophages (M{phi}) to express iNOS shows extreme interspecies variability. Here the expression of iNOS and synthesis of NO was studied in listeric encephalitis of cattle, sheep, and goats. iNOS was expressed by a subset of M{phi} in cerebral microabscesses in all three species. The level of iNOS expression and the density of cells per lesion expressing iNOS was highest in cattle, intermediate in sheep, and lowest in goats. The accumulation of nitrotyrosine (NT), an indicator of local NO synthesis, was observed in lesions of cattle but not in those of small ruminants. The density of iNOS-expressing cells in lesions was inversely correlated with the number of bacteria. No species differences were observed in regard to reactive oxygen intermediate (ROI) production by stimulated granulocytes, using the flow cytometric dihydrorhodamine-123 (DHR) method indicating ROI generation. Thus, the marked species differences in iNOS expression, NT accumulation, and LM content in lesions of ruminants with listeric encephalitis are explained by different amounts of ROI produced. It suggests that variations in the ability of M{phi} to synthesize NO are of pathophysiological significance in listeriosis.

Key words: Brain; cattle; sheep, goat; Listeria monocytogenes; nitric oxide; nitric oxide synthase; nitrotyrosine.

Request reprints from T. W. Jungi, Institute of Veterinary Virology, University of Berne, Laenggassstrasse 122, CH-3012 Berne (Switzerland).




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