Masters Thesis

Innate immunity of the nematode worm Caenorhabditis elegans, its interaction with the bacterial pathogen Burkholderia thailandensis, and the nature of defensin-like peptides

The science of immunology, for much of its history, has focused on the ability to induce the biological acquisition of specific immunity or on the ability to produce specific immune agents. Examples are, respectively, vaccinations that enable vertebrate animals to become completely immune to a specific microbe, and production of specific antiserums and antibodies that can be used to directly treat illness, or to study cellular biology. In modern times a new appreciation for non-adaptive immune measures, a.k.a. innate immunity, has begun to emerge. It has become increasingly clear that non-adaptive measures carry out a massive portion of the work done in keeping multicellular organisms immune. This work includes the quintessential functions of self/non-self recognition and initiation of adaptive responses. In the last ten years the nematode worm Caenorhabditis elegans has begun to be used as an effective model organism for the study of innate immunity. It has been shown that this worm engages in recognition of pathogens via pathogen associated molecular patterns (PAMPs), that it uses conserved cellular signaling pathways during its immune response, that it constitutively produces conserved microbicidal measures, and that it responds to infections by inducing expression of conserved microbicidal effectors. In the current study I have exposed C. elegans to the bacterial pathogen Burkholderia thailandensis, which is a nearly identical pathogen to the causative agent of the human disease Melioidosis (Burkholderia pseudomallei). I did this in an effort to shed some light on the nature of this infection. Specifically, I exposed C. elegans worms to living bacteria and to bacterial exometabolites. I then measured the expression of genes known to be involved in the worm’s immune function. In addition, I compared the CSαβ-type (defensin-like) peptides of this worm to putative protein sequences from the human genome and discovered a high degree of identity in some examples. My results show that the worm is responding immunologically to B. thailandensis and that this microbe’s exotoxic effects are having direct impact on the worm’s expression of at least one CSαβ-type peptide. In addition, my results suggest that there may be a class of CSαβ-like peptide that has been previously uncharacterized.