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  1. M. N. Paddock,
  2. K. Graef,
  3. H. Clay,
  4. C. L. Cosma,
  5. L. Ramakrishnan
  1. Department of Microbiology, University of Washington, Seattle, WA


Tuberculosis is a major and growing problem worldwide, and much effort has gone into understanding the pathogenesis of the disease. One of the perplexing issues is the role of macrophage apoptosis in vivo. Apoptosis of cultured macrophages has been observed in response to infection; however, the relevance of this response in vivo is unclear, and there are conflicting reports on whether apoptosis is more beneficial to the bacteria or the host. The Mycobacterium 19 kDa lipoprotein is a potent inducer of macrophage apoptosis in vitro and so we wanted to examine the role of this protein in vivo. To do this we used a M. marinum-zebra fish infection model of mycobacterial pathogenesis and compared the ability of wild-type versus 19 kDa lipoprotein-deficient (lpqH-) bacteria to induce apoptosis. We examined induction of apoptosis in a murine macrophage cell line (J774) and in zebra fish embryos using TUNEL labeling with fluorescent microscopic and flow cytometric analysis of the murine macrophages and TUNEL labeling with fluorescent microscopic examination of the embryos. Results suggest that the level of apoptosis induced by infection with the lpqH- strain of M. marinum was not reduced compared to the level of apoptosis induced by infection with the wild-type M. marinum in the murine macrophages. In the zebra fish embryos, Mycobacterium-induced granulomas infected with the lpqH- strain were not any less likely to be TUNEL + than the aggregates formed in response to the wild-type infection (p = .47), but the number of TUNEL + cells in each aggregate was slightly lower in the lpqH- infection (p = .018). Taken all together, these results lead us to believe that the lpqH gene in M. marinum is not necessary to induce apoptosis in macrophages in vitro or in vivo.

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