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Characterization of a Novel Bacterial PAMP and its interaction with C-type Lectin Receptor Dectin-1

Pedro, Sílvia Catarina (2021) MOBN03 20201
Degree Projects in Molecular Biology
Popular Abstract
Interactions of a potential new PAMP with a startling receptor

The presence of an innate immune system means we are able to quickly identify a threat and promptly fight it off without the need to ask for its identification card. This way, innate immunity dampens damage while providing time for the adaptive branch of the immune system to develop more specific cells and molecules against the intruder. To accomplish this, innate immune cells rely on the recognition of highly conserved structures of potentially infectious organisms, known as pathogen-associated molecular patterns (PAMPs). Such molecules are recognized by different receptors in the cells membranes, and are referred to as pattern recognition receptors (PRRs). Dectin-1 is one... (More)
Interactions of a potential new PAMP with a startling receptor

The presence of an innate immune system means we are able to quickly identify a threat and promptly fight it off without the need to ask for its identification card. This way, innate immunity dampens damage while providing time for the adaptive branch of the immune system to develop more specific cells and molecules against the intruder. To accomplish this, innate immune cells rely on the recognition of highly conserved structures of potentially infectious organisms, known as pathogen-associated molecular patterns (PAMPs). Such molecules are recognized by different receptors in the cells membranes, and are referred to as pattern recognition receptors (PRRs). Dectin-1 is one of these receptors and its ability to recognize carbohydrates differentiate it from other such receptors, which usually bind pathogenic proteins instead.

Denoted protein X is an essential protein which amounts for a large bulk of the cytoplasmic proteins in bacteria. It is highly conserved and, importantly, is also present on the surface of many different bacterial species, where it serves multiple functions. In pathogens, it is a factor of increased virulence and is involved in invasion of host cells. Such characteristics led us to believe that this protein might thus be recognized by innate immune cells as a bacterial PAMP.

On the other hand, Dectin-1 is a PRR so far only known to recognize components of fungal cell walls, against which it activates an immune response. The lab has, however, shown previously that protein X interacts with Dectin-1. With this project we focused thus on investigating if protein X is a PAMP capable of triggering strong innate immunity upon recognition by Dectin-1.

Can Protein X be a pathogen signature recognized by Dectin-1?
To test this, we started by producing protein X from different bacterial species and confirming all were bound by Dectin-1. Next we used the protein to stimulate modified human cell lines. This way, we were able to look at differences in the response to the protein in cells overexpressing Dectin-1 as opposed to cells without the surface receptor. Finally we went onto stimulating mouse naïve immune cells with protein X and comparing specific markers of activation in both cells expressing all the receptors and cells lacking only Dectin-1.

Our results show that Dectin-1 does bind protein X from different bacterial species. The data collected shows also activation of immune cells upon stimulation with the protein, but one specific inflammation marker was produced on a similar matter by both cells expressing Dectin-1 and cells lacking the receptor. However, we saw that protein X was incapable of stimulating human cells which had Dectin-1 as the only surface PRR, suggesting another receptor might work together with Dectin-1 and be involved in the response to the protein. The project opens the possibility to explore the interaction between protein X and Dectin-1 further, as well as with other PRRs.

Master’s Degree Project in Molecular Biology 60 credits 2021
Department of Biology, Lund University

Supervisors: Oskar Thofte, Prof. Kristian Riesbeck
Clinical Microbiology, Department of Translational Medicine, Lund University, Malmö (Less)
Please use this url to cite or link to this publication:
author
Pedro, Sílvia Catarina
supervisor
organization
course
MOBN03 20201
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9039023
date added to LUP
2021-02-01 15:59:15
date last changed
2021-02-01 15:59:15
@misc{9039023,
  author       = {Pedro, Sílvia Catarina},
  language     = {eng},
  note         = {Student Paper},
  title        = {Characterization of a Novel Bacterial PAMP and its interaction with C-type Lectin Receptor Dectin-1},
  year         = {2021},
}