Submitted to: Society for Leukocyte Biology Meetings Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 9/16/1995
Publication Date: N/A
Technical Abstract: As a primary pulmonary infection, cellular models have been developed to study the pathogenesis of tuberculosis (TB). The immune cell largely responsible for the pathogenesis of pulmonary TB infection is the alveolar macrophage (AM). We describe AM heterogeneity and show in vitro susceptibility to TB infection differs between AM subpopulations. Using pigs as an animal model for TB, we determined whether AM subpopulation status following M. bovis infection related to severity of infection. AM were obtained from M. bovis-infected pigs by lavage at 30, 45 and 60 d post infection and were separated by Percoll gradient centrifugation. We consistently observed a shift in the AM subpopulations at the three time points and at several doses, such that the least mature, most monocyte-like AM were not present and the majority of cells accessible by lavage were of the most mature, fully-activated phenotype. This in vivo result is supported by our finding that in vitro susceptibility to infection decreased as the maturation state of the AM increased. The status of AM subpopulations within the lungs of infected pigs is associated with disease severity, as evaluated by clinical signs and extent of lesions. We are currently performing experiments to determine whether the shift is the result of activation of infected cells, or the elimination of the infected subpopulation.