Mycobacterium marinum (Mm) shares at least 80% amino acid sequence identity with over 3,000 orthologous genes of Mycobacterium tuberculosis (Mtb) and is thus used as a surrogate pathogen for Mtb research. Our laboratory investigates mycobacteriosis using Japanese medaka ( Oryzias latipes) as an aquatic animal model. Mm disease presentation in medaka is similar to Mtb disease presentation in humans, including growth in macrophages, granulomatous lesions, and lifelong chronic disease. We have previously shown that a major route of infection in fish is through an oral route and have thus developed methods to infect medaka with Mm utilizing mosquito larvae as vectors. Recently, our lab was able to show that Mm is able to cross the gut epithelia of medaka in a relatively short-time frame and travel to the underlying submucosa. Therefore, Mm must have the ability to attach to the gut mucosal layer and evade killing by GALT immune cells. Mm is apparently able to exploit macrophages of the mucosal immune system to transport the bacteria to target organs like the head kidney, liver, and spleen for a systemic infection. Utilizing an Mm strain engineered to carry a deletion in the RD-1 region, known to include a number of virulence genes, our lab has shown that mucosal immunity against Mm can be induced in medaka. We have shown that exposure to the mutant RD-1 strain offers some protection against a chronic wild-type oral challenge. Since we know that mutant RD-1 can elicit a mucosal immune response, I tested to see if sensitizing mucosal immunity would also induce systemic immunity by first priming fish with mutant RD-1 and then subsequently challenging them with wild type Mm via an IP route. This thesis demonstrates that mucosal immunity is limited to the gut and thus does not appear to provide broad systemic immunity. Additionally, I tested to see if systemic vaccination would protect against a systemic virulent wild-type challenge by vaccinating and challenging fish via an IP route of infection. Results showed that systemic vaccination does not induce systemic immunity and thus does not protect against an IP injected virulent challenge. Collectively, results from this thesis have shown mutant RD-1 to only be effective as a vaccine against mycobacteriosis if given orally since it was shown to only induce a mucosal immune response and only be protective against an oral virulent wild type challenge.
|Advisor:||Ennis, Don G.|
|Commitee:||Chistoserdov, Andrei Y., Watson, Glen M.|
|School:||University of Louisiana at Lafayette|
|School Location:||United States -- Louisiana|
|Source:||MAI 56/02M(E), Masters Abstracts International|
|Keywords:||Aedes aegyti, Mucosal immunity, Mycobacterium marinum, Oreochromis niloticus, Oryzias latipes, Systemic immunity|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be