1887

Abstract

Latency and reactivation are a significant problem that contributes to the incidence, transmission and pathogenesis of tuberculosis. The mechanisms involved in these processes, at the level of both the bacillus and the host, are poorly understood. In the -crystallin () gene has been linked to latency, because it is highly expressed during hypoxic growth conditions. Deletion of the gene in H37Rv (Δ strain) was previously shown to reduce the intracellular growth of bacilli in macrophages; however, its impact on pathogenesis was unknown. This study demonstrated that infection of C57BL6 mice with Δ results in lung bacillary loads 1-2 log units higher in comparison to parental H37Rv. Haematoxylin/eosin staining of lungs revealed exacerbated pathology characterized by extensive obliteration of alveolar air spaces by granulomatous inflammation. RT-PCR analysis and immunostaining of lungs showed that infection with either H37Rv or Δ results in the differential expression of lysosomal cathepsin proteases. A slight increase in the expression of the matrix-degrading acidic-type cathepsins B, D and H was noted in Δ-infected mice and was associated with clusters of macrophages within lung granulomas. Δ-infected mice also showed high serum levels of TNF-, IFN- and G-CSF, suggesting that Acr may play a role in modulating the host response to infection.

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2006-01-01
2019-10-24
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