Local Production of Tumor Necrosis Factor-α in Corynebacterial Pulmonary Lesions in Sheep

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Abstract
Corynebacterium pseudotuberculosis infection is a common cause of pyogranulomas in ovine lungs and often occurs as a dual infection with lentiviruses. This coinfection usually leads to the development of chronic pneumonia and cachexia that is similar to the clinical syndrome seen in human beings with AIDS-related pneumonias. Recent in vitro studies indicate that monokines such as tumor necrosis factor-α (TNFα) are induced by C. pseudotuberculosis, suggesting that TNFα is involved in the pathogenesis of corynebacterial lesions in vivo. To substantiate in vitro observations concerning bacterial induction of TNFα in ovine pulmonary macrophages, immunohistochemical labeling techniques were used in combination with in situ hybridization to identify TNF-producing cells in corynebacterial lesion sites in vivo. TNFα message and translation product were found in macrophages comprising pyogranulomas that were induced by naturally acquired and experimental pulmonary C. pseudotuberculosis infections.