The interaction of microbes with dendritic cells (DCs) is likely to have an enormous impact on the initiation of the immune response against a pathogen. In this study, we compared the interaction of Mycobacterium tuberculosis with murine bone marrow derived DCs and macrophages in vitro. M. tuberculosis grew equally well within non-activated DCs and MØ. Activation of DCs and MØ with IFN-g and LPS inhibited the growth of the intracellular bacteria in an NOS2-dependent fashion. However, while this activation enabled MØ to kill the intracellular bacteria, the M. tuberculosis bacilli within activated DCs were not killed. Thus, DC could restrict the growth of the intracellular mycobacteria, but were less efficient than macrophages at eliminating the infection. These results may have implications for priming immune responses to M. tuberculosis. In addition, they suggest that DCs may serve as a reservoir for M. tuberculosis in tissues, including lymph nodes and lungs.
Dendritic cells (DC) possess anti-microbial mechanisms that may play a role in M. tuberculosis infection. Activated DC and MØ produce a comparable amount of reactive nitrogen intermediates, as measured by nitrite production but our data indicate that nitric oxide production is not directly responsible for the differences in the ability of DC and MØ to kill M. tuberculosis. Activated DC have the capacity to produce greater quantities of (reactive oxygen intermediate) ROI than activated MØ. The higher levels of ROI in infected DC may affect the formation of different (reactive nitrogen intermediate) RNI species, such as peroxynitrite, and alter the lethal effect on M. tuberculosis. In addition DC may not able to acidify their phagosomal compartment, where the bacilli reside, to the same degree as macrophages. This may contribute to the ineffectiveness of their anti-microbial compounds.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-02012002-001016 |
| Date | 26 April 2002 |
| Creators | Bodnar, Kendra Anne |
| Contributors | Dr. Michael Murphy-Corb, Dr. Charles Rinaldo, Dr. Simon Barrat-Boyes, Dr. Walter Storkus, Dr. Karen Norris, Dr. JoAnne Flynn |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu:80/ETD/available/etd-02012002-001016/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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