Characterisation of paired C-type lectins as receptors for Myzocytiopsis humicola and Haptoglossa zoospora recognition in Caenorhabditis elegans
File(s)
Author(s)
Liu, Ka Chun
Type
Thesis
Abstract
To protect itself against pathogens, Caenorhabditis elegans relies on innate immunity and is able to mount defensive, pathogen-specific transcriptional responses in the absence of infection. However, how C. elegans recognizes different pathogens is unclear, as they lack many of the canonical pattern recognition receptors found in other organisms. In this study, I utilize two natural oomycete pathogens of C. elegans, Myzocytiopsis humicola and Haptoglossa zoospora and characterize how C. elegans recognizes and responds to them. I identify the intestine and the AWA neurons as tissues where M. humicola is recognized by the C-type lectin receptors CLEC-27/35 and where H. zoospora is recognized by CLEC-26/36. I provide further evidence of homeodomain transcription factor involvement in immunity, where the homeodomain transcription factor CEH-37 is required for oomycete recognition as it regulates the expression of clec-27/35 and clec-26/36. I demonstrate that CLEC-mediated oomycete recognition lies upstream of previously identified epidermal signalling mediated by OLD-1/FLOR-1, and that neuropeptide signalling is not required for cross-tissue communication of oomycete recognition from the intestine and neurons to the epidermis. I characterize the transcriptional response induced in C. elegans upon Haptoglossa recognition, finding upregulation of genes involved in cuticle structure and innate immunity. In addition to this, I show that upregulation of the serine protease inhibitor Y9G5A.1 is a Haptoglossa-specific defence response by C. elegans which can increase survival against H. zoospora infection, potentially by inhibiting secreted proteases, which I identify as likely H. zoospora effectors. Lastly, I identify two new Haptoglossa isolates JUo7 (H. heterospora) and JUo8 (Haptoglossa sp.) and show that the requirement of CLECs for Haptoglossa recognition can differ between isolates. Overall, these findings contribute towards understanding of how pathogen specific recognition and response occurs in C. elegans and establish CLEC proteins as receptors for pathogen recognition in C. elegans.
Date Issued
2025-01-30
Date Awarded
01/06/2025
License URL
Advisor
Barkoulas, Michalis
Sponsor
Biotechnology and Biological Sciences Research Council (Great Britain)
Publisher Department
Department of Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)