Macrophages play a critical role in innate immunity by detecting, engulfing and destroying pathogenic bacteria and alerting neighbouring immune cells to join the fight against infection. They have many different receptors on their cell surface that allow them to carry out these important processes. A particular group of receptors called Scavenger Receptors are vital to this response. A recent study published in Immunology and Cell Biology by PhD student Kyle Novakowski from the laboratory of Dr. Dawn Bowdish has uncovered a mechanism by which a specific scavenger receptor contributes to macrophage-specific antibacterial immunity.
Scavenger Receptors are evolutionarily ancient and have evolved to recognize a wide array of pathogens by detecting ligands that are common across many pathogenic organisms. A particularly important Scavenger Receptor is Macrophage Receptor with Collagenous Structure, or MARCO. MARCO has been shown to significantly contribute to the clearance of Streptococcus pneumoniae colonization of the nose and in models of pneumococcal pneumonia. The NSERC-funded study took a unique approach to functionally characterizing how MARCO contributes to innate immunity by studying a naturally-occurring variant of the receptor. The study highlighted the importance of a particular domain of the receptor that is required for macrophages to bind and internalize ligands. The study also showed that the domain is necessary to enhance the pro-inflammatory response to pathogenic Streptococcus pneumoniae and can enhance cellular adhesion; both vital to proper macrophage functions.
The Bowdish lab is thrilled to participate in NSERC’s “Science, Action!” video contest. An undergraduate team of videographers (Yung Lee, Karanbir Brar, and Tony Chen) filmed our lab discussing our NSERC funded work on discovering the evolutionary origins of phagocytosis. Please “like” and share our video to help us move on to the next level of the competition.
Our NSERC funding has been integral to the lab. This was one of the first grants that got the lab up and running and to date we have had 5 NSERC funded graduate students and 10 undergraduate students including 3 NSERC Undergraduate Summer Research Assistants in the lab. This funding has also been instrumental in developing new techniques, technologies and collaborations that have extended our research capacity.
What are we studying with our NSERC funded research?
Our NSERC Discovery Grant entitled “Uncovering mechanisms of phagocytosis by class A scavenger receptors” allows us to use bioinformatics and molecular biology to understand the very origins of immunity.
Our lab studies macrophages, which are sentinel cells of the innate immune response. They patrol the body and engulf damaged tissues or pathogens and destroy them. This Pac-man like ability to eat microbes is called “phagocytosis”. We study a particular class of receptors that macrophages use to phagocytose called the scavenger receptors.
Phagocytosis is an ancient process that is central to defence and nutrient acquisition in single-celled organisms and embryonic development, clearance of modified host proteins and innate immunity in multi-cellular organisms. During phagocytosis a phenomenal amount of information is transmitted to the cell including the size and shape of the particle, its composition, and potential toxicity. How this information is transmitted is not really understood but is the focus of our work.
All the major discoveries in immunology (e.g. toll like receptors, intracellular sensors, signalling pathways) began with studies in comparative or evolutionary biology and my program of research continues this tradition. Indeed, the process of phagocytosis is believed to be the prototype function of the immune system as acquisition of nutrients developed into a mechanism of self- versus non-self recognition. The process of uptake is so ancient that it must have occurred prior to or in conjunction with the expression of protein receptors on the surface of the cell. The scavenger receptors, being primitive but effective uptake receptors may rely on membrane dynamics and lipid interactions more than their more evolutionarily recent counterparts (e.g. Fc receptors). We use bioinformatics to study the genomes of ancient and modern animals to study how the scavenger receptors change over time. Parts of the scavenger receptor gene or protein that haven’t changed over time, are likely very important for function. We use molecular biology to uncover how these particular regions of the protein work. Studying these processes will uncover novel mechanisms of signalling and contribute to our understanding of the cell biology of endocytosis and phagocytosis, which are processes integral to embryonic development, immunity, homeostasis, implant recognition and adhesion and consequently essential to many fields of biology.
Check out the other videos of the “Science, Action!” video contest here.
Do you work out? Cause you’re built like a rock! A rock like Dwayne “The Rock” Johnson! You have an impenetrable body thanks to your complex immune system. So how did you get such a sophisticated immune system?
In the Bowdish lab, we do more than just macrophage biology; we also study the evolution of the immune system! The scavenger receptors are a group of receptors that play an important role in your immune system by binding harmful bacteria. Our most recent publication by Yap et al., looks at how these receptors evolved and how evolution has changed their function. These receptors are found in various forms of life such as sharks, frogs, and mammals, but the function and appearance of these receptors has changed over time. Check out the open access….
Avee Naidoo successfully passed her transfer exam today. She now joins the ranks of Fan Fei, Mike Dorrington, Kyle Novakowski, Dessi Loukov, Sara Makaremi, and Pat Schenck as part of the Bowdish lab PhD posse. Well done Avee!
Becoming a PhD student in the Bowdish lab is a family affair. Junior lab members sent their favourite stuffie in to wish Avee luck. It must have worked as she aced it!
…and a little lab humour. We have both skilled scientists (see picture at bottom) and skilled artists (see whiteboard) in our lab.
We’ve added some major new protocols to the protocol section. We know have a section on basic molecular biology, some protocols for 16s rRNA sequencing, some updates to our transfection and NF-kB reporter protocols, etc. Take a gander & enjoy.
The nose is the gateway to the soul… or the lungs at least… making it an important point of first contact between our fragile bodies and the hordes of superbugs attempting to take over the world. Only the brave immunologist has the power to save us from this dire threat. While it’s been known for a few years now that the inflammatory cytokine IL-17A is key to the control of many respiratory infections, no-one has been able to provide any information on the source of this cytokine in nasal infections or how this production is regulated. No more!
Post-doctoral fellow Chris Verschoor and Ph.D. Candidate Mike Dorrington, both trainees in Dr. Dawn Bowdish’s lab have recently had their manuscript “MicroRNA-155 is required for the clearance of Streptococcus pneumoniae from the nasopharynx” accepted for publication in Infection & Immunity. The paper, which was produced in collaboration with Dr. Param Nair of the Firestone Institute, outlines how microRNA- (miR-)155 regulates the immune response to S. pneumoniae colonization in the nasal passages of mice by stimulating the differentiation of Th17 cells. These cells then produce large amounts of IL-17A, which then acts as a chemotactic agent for macrophages, which have awesome swords and stuff that kill the bacteria and save the world! (macrophages are the best cells, by the way)
This paper is the first to show a direct connection between IL-17A-producing T cells and the clearance of a bacterial pathogen from the nasopharynx. It is also the first to show a phenotype of IL-17A deficiency without completely knocking out the cytokine itself. It represents a significant step forward in understanding the regulation of intranasal immune responses to bacterial colonization and how innate and adaptive immune networks collaborate in clearing these events. Way to go Bowdish Lab!
For more information please visit www.bowdish.ca/lab and check out the paper in an upcoming edition of Infection & Immunity.
This paper demonstrates that there are host- and strain- specific responses to isolates of the Streptococcus milleri/anginosis group and that isolates from invasive disease appear to be more immunostimulatory than those from commensal relationships.