BACTERIAL METABOLISM, CYTOKINE MESSENGER-RNA TRANSCRIPTION AND VIABILITY OF BOVINE ALVEOLAR MACROPHAGES INFECTED WITH MYCOBACTERIUM-BOVIS BCG OR VIRULENT M-BOVIS

Mycobacterium bovis causes tuberculosis in cattle and many other anima ls including humans while BCG, an attenuated form of M. bovis, has bee n used widely as a safe vaccine. Both strains infect host macrophages and their fate is determined by their ability to survive within these phagocytic cells. We compared interactions of these two strains with b ovine alveolar macrophages in order to gain an understanding of virule nce mechanisms involved in the early pathogenesis of M. bovis infectio n. Macrophages were infected with bacilli at varying multiplicities of infection and cultured for 1-4 days. Bacterial metabolism within macr ophages was assessed by [H-3]-uracil uptake and bacterial growth was a ssessed by culture and acid-fast staining. Induction of TNF-alpha, IL- 1 beta and IL-6 cytokine mRNA transcription in macrophages was determi ned by reverse transcriptase-polymerase chain reaction. Infection of m acrophages by virulent M. bovis resulted in enhanced bacterial metabol ism, enhanced induction of macrophage cytokines and reduced viability of macrophages when compared to M. bovis BCG-infected macrophages. The se differences may reflect virulence mechanisms contributing to the ea rly pathogenesis of bovine tuberculosis.