Potential Roles of Peroxidases In Caenorhabditis Elegans Innate Immunity

<p>The production of ROS (reactive oxygen species) in response to pathogen detection is a rapid, nonspecific response that is evolutionarily conserved from nematodes to humans. ROS serve as direct and indirect effectors of innate and adaptive immunity. In <em>Caenorhabditis elegans</em>, a ROS burst is observed during infection and is mediated by the dual oxidase BLI-3, which produces H₂O₂. RNAi (RNA interference) to reduce the amount of BLI-3 results in a significant increase in susceptibility to pathogens, suggesting BLI-3 has a role in the immune response. However, H₂O₂ by itself is not a potent antimicrobial and in other systems is converted to a more potent oxidant by an affiliated peroxidase. During my work, I have characterized a group of previously unstudied peroxidases in <em>C. elegans </em>and determined their involvement in the host immune response to <em>Enterococcus faecalis</em>. In particular, I focused on SKPO-1 (ShkT-containing peroxidase) and how it contributes to the host immune response with respect to BLI-3.</p> <p>By RNAi and <em>skpo-1</em> mutant analysis, I determined that SKPO-1 is involved in the host immune response during <em>E. faecalis</em> infection. By tissue-specific RNAi, I determined that SKPO-1 is functionally active in the hypodermis and required for wild type resistance to infection. Additionally, by immunohistochemistry, I observed that SKPO-1 is only expressed in the hypodermis and that its protein levels do not change in response to <em>E. faecalis</em>. In support of SKPO-1 acting as a peroxidase, I observed a significant increase in H₂O₂ levels when expression of the gene was reduced by RNAi. The increased H₂O₂was observed only during infection and was BLI-3-dependent. Thus, I have characterized a likely BLI-3/SKPO-1 system, potentially similar to the oxidative burst systems present in higher eukaryotes.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2014

Author dc:creator

• Tiller, George R

Contributors dc:contributor

• Danielle A. Garsin
• Joseph Alcorn
• Steve Norris

• Peroxidase
• SKPO-1
• ROS
• innate immunity
• E. faecalis
• C. elegans
• hypodermis
• Immunity
• Medicine and Health Sciences
• Molecular Genetics
• Pathogenic Microbiology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/483

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1523