Bodnar, Kendra Anne
(2002)
The Interaction between Murine Dendritic Cell and Mycobacterium tuberculosis.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
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.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | Flynn, JoAnne | joanne@pitt.edu | JOANNE | | | Committee Member | Rinaldo, Charles | | | | | Committee Member | Norris, Karen | kan1@pitt.edu | KAN1 | | | Committee Member | Murphy-Corb, Michael | mcorb@pitt.edu | MCORB | | | Committee Member | Barrat-Boyes, Simon | smbb@pitt.edu | SMBB | | | Committee Member | Storkus, Walter | | | |
|
| Date: |
26 April 2002 |
| Date Type: |
Completion |
| Defense Date: |
3 January 2002 |
| Approval Date: |
26 April 2002 |
| Submission Date: |
1 February 2002 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Infectious Diseases and Microbiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
anti-microbial; nitric oxide; peroxynitrite |
| Other ID: |
http://etd.library.pitt.edu:80/ETD/available/etd-02012002-001016/, etd-02012002-001016 |
| Date Deposited: |
10 Nov 2011 19:31 |
| Last Modified: |
15 Nov 2016 13:36 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/6320 |
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