Helicobacter pylori infection persists for the life of the host due to the failure of the immune response to eradicate the bacterium. Determining the mechanisms by which the bacterium escapes the immune response are clinically important. Our aim was to determine if induction of arginase II (Arg2) by H. pylori modulates host defense. We have demonstrated that macrophage nitric oxide production can kill H. pylori; however, induction of macrophage Arg2 inhibits inducible nitric oxide synthase (iNOS) translation, induces apoptosis, and restricts bacterial killing. After 4 mo infection with H. pylori, we found that enhanced gastritis correlated with decreased bacterial colonization in Arg2/ mice, but not WT mice. We found that iNOS+ macrophages were more abundant in Arg2/ mice, less apoptotic, and had increased nitrotyrosine staining. This correlated with enhanced pro-inflammatory cytokine production. These studies suggest that Arg2 mediates the immune evasion of H. pylori by restricting macrophage function.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-02022011-214404 |
| Date | 15 February 2011 |
| Creators | Lewis, Nuruddeen |
| Contributors | Timothy S. Blackwell, Timothy L. Cover, Luc Van Kaer, Barbara Fingleton, Keith T. Wilson |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-02022011-214404/ |
| 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 Vanderbilt University 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. |
Page generated in 0.0019 seconds