Kyle Novakowski successfully defended his thesis “IDENTIFICATION AND FUNCTIONAL CHARACTERIZATION OF CONSERVED RESIDUES AND DOMAINS IN THE MACROPHAGE SCAVENGER RECEPTOR MARCO” to become the Bowdish lab’s 4th PhD student. He’ll be joining Turnstone Biologics as a PhD scientist. We wish him very well in his future endeavours. Congratulations Dr. Novakowski!
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
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.
Novemer 12th is World Pneumonia Day – celebrate by getting vaccinated against influenza and pneumococcal pneumonia!
Hear the interview on Metro Morning with Matt Galloway here:
Read about why older adults should be vaccinated against pneumococcal pneumonia and influenza, as profiled by the CBC here:
To hear Dawn discuss the benefits of vaccination for older adults on London AM 960 The Pulse with Devon Peacock (airdate: Nov 13, 2015) click here:
To read about the link between dementia and pneumonia:
To read about the link between cardiovascular disease and pneumonia
Work in the Bowdish lab is funded by the Canadian taxpayer through the Canadian Institutes of Health Research, the National Science and Engineering Research Council, and through donations administered by the Ontario Lung Association.
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.
Verschoor CP, Dorrington MG, Novakowski KE, Kaiser J, Radford K, Nair P, Anipindi V, Kaushic C, Surette MG, Bowdish DME. MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx. Infect Immun. 2014 Nov;82(11):4824-33. doi: 10.1128/IAI.02251-14.
This paper 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.
Kaiser JC, Verschoor CP, Surette MG, Bowdish DME. Host cytokine responses distinguish invasive from airway isolates of the Streptococcus milleri/anginosis group. BMC Infect Dis. 2014 Sep 11;14:498. doi: 10.1186/1471-2334-14-498.
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.