Colonization of Streptococcus pneumoniae within the upper respiratory tract (URT) of elderly individuals is a major concern, as it often results in the development of pneumonia, which can be deadly in this population. A study published by MIRC Masters’ student Netusha Thevaranjan, under the supervision of Dr. Dawn Bowdish, examined how aging can change the composition of the respiratory microbial community and consequently, impact bacterial colonization. Using a mouse model of pneumococcal colonization, the study characterized the composition of the URT microbiota in young, middle-aged, and old mice in both the naïve state, and throughout the course of nasopharyngeal colonization with S. pneumoniae. It was shown that the composition of the URT microbiota differs with age, and that colonization with S. pneumoniae in older mice disrupted pre-existing microbial communities.
Furthermore, the study demonstrated that there were several interspecies interactions between S. pneumoniae and resident microbes. In particular,Streptococcus interacted competitively with Staphylococcus and synergistically with Haemophilus. This work provides insight into how aging influences bacterial colonization, and understanding the relationship between these two factors can help create strategies to protect the elderly from age-associated infections and disease. Read More
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.
Antibiotic treatment alone may not be sufficient to treat pneumonia in older adults. In fact, it appears as though the inflammation that comes naturally with age increases the risk of developing pneumonia. “It sounds counterintuitive to limit inflammatory responses during a bacterial infection, but clinical observations and our research indicates anti-bacterial strategies need to be tailored to the age of the patient,” said MIRC’s Associate Professor Dawn Bowdish.
Aging is accompanied by a chronic state of low-level inflammation — sometimes called ‘inflamm-aging’ — which is associated with diseases such as cardiovascular disease, dementia and infections, particularly pneumonia. Upon recognition of an infectious agent, an acute inflammatory response is required to fight infection and resolves shortly after. However, in older adults, where systemic inflammation is already elevated, increases in inflammation during infection do not resolve as quickly. Exposure to these high levels of inflammation appears to impair the ability of monocytes and macrophages to fight infection.
Published today in the journal PLoS Pathogens, MIRC graduate Dr. Alicja Puchta & PhD student Avee Naidoo demonstrated that the higher levels of inflammation in the blood of old mice caused the premature egress of inflammatory monocytes into the blood stream, and contributed to greater systemic inflammation. Although small amounts of inflammation are required to fight infection, enhanced production of inflammation in old mice lead to reduced monocyte and macrophage function. Reducing levels of inflammation in the young mice had no effect but reducing levels in the old mice resulted in improved bacterial clearance and survival against S.pneumoniae.
The research follows a 2015 McMaster study that showed that older adults with pneumonia do better when given drugs, such as corticosteroids, to reduce inflammation in addition to antibiotics. “Our study in mice is consistent with clinical studies that recommend using anti-inflammatories as part of treatment to improve older adults’ defence against pneumonia, and that points to the development of better care,” said Bowdish.
To read the PLoS Pathogens article, please click here.
We are in the enviable position of being a popular lab and have received a large number of applications for a very small number of positions. We thank you for your interest but I’m afraid that we are no longer accepting applications but wish all the undergraduates searching for summer/thesis positions the very best of luck in their search.
aging can change the composition of the respiratory microbial community and consequently, impact bacterial colonization. Using a mouse model of pneumococcal colonization, the study characterized the composition of the URT microbiota in young, middle-aged, and old mice in both the naïve state, and throughout the course of nasopharyngeal colonization with S. pneumoniae. It was shown that the composition of the URT microbiota differs with age, and that colonization with S. pneumoniae in older mice disrupted pre-existing microbial communities.
