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.
Research in Lung health is not nearly as well funded as it should be considering the toll it takes on patients and our healthcare system. That’s why the Bowdish lab is involved in the Lung Association’s Breathing as One campaign to raise money for lung research. Click on the picture to read the insert that was delivered in a number of newspapers (including our own Hamilton Spectator) to launch the campaign.
This past month has been very productive in the Bowdish laboratory, with many triumphs achieved by it’s industrious members.
Firstly, a big congratulation goes to Kyle Novakowski, the Bowdish lab’s newest PhD student. Following a lot of hard work, determination and great dedication to his Masters project, Kyle successfully passed his transfer exam on July 7 and has officially begun his
seemingly endless exciting pursuit for a PhD. Good luck to Kyle in continuing his interesting investigation on the regulation and function of MARCO!
Next up is Dessi Loukov, who is currently an undergraduate but come September will be the Bowdish lab’s 4th PhD student. At the 1st annual MIRC Perey Symposium held on June 19, Dessi impressed faculty and trainees with her educational and enthusiastic speed poster presentation on modulating the immune system to potentially reverse age-associated inflammation. Dessi was awarded a travel award as a result of her superb presentation skills. Kudos also to Fan Fei (PhD candidate) and Avee Naidoo (MSc candidate) who gave excellent speed poster talks and Dr. Chris Verschoor who gave an excellent oral presentation. Who knew that research in inflammation could be so exciting? The Bowdish lab, that’s who!
One PhD candidate who deserves great recognition for his recent successes is Mike Dorrington. Not only was Mike awarded with a prestigious and well-deserved Canadian Lung Association & Canadian Thoracic Studentship, but he additionally achieved received The Ruth and Wilson Tafts Prize for Immunology for having the best paper published in a peer-reviewed journal in 2013. Geez Mike, save some awards for the rest of us. These awards will be used to further fund his fascinating work on the role of macrophages – clearly, the best cell around – in recognition and clearance of Streptococcus pneumoniae in the upper respiratory tract. Congratulations Mike!
Then, there’s Dr. Chris Verschoor, the lab’s most productive and well-rounded member. Chris’ paper entitled, “Alterations to the frequency and function of peripheral blood monocytes and associations with chronic disease in the advanced-age, frail elderly“, was recently accepted into the PLoS one. If you’re interested in changes in monocyte populations with age – I mean, who isn’t? – keep a look out for Chris’ article in the next issue of PLoS one . Way to go Chris on this well-deserved publication!
<- Manuscipt accepted = happy post-doc.
And last, but definitely not least, the lab takes great pleasure in congratulating our passionate leader, Dr. Dawn Bowdish, who has been awarded tenure and a promotion to Associate Professor effective as of July 1, 2014. This accomplishment is a fitting acknowledgement of Dawn’s exceptional work, devotion and academic contributions to research in the field of macrophage biology. In addition to her promotion and tenure, Dawn recently received a Best Teacher Award in the Department of Pathology for excellence in undergraduate teaching and graduate supervision. Well-done Dawn!
Congratulations Bowdish lab on our successes!
Way to kill it, like young macrophages on pneumo 😉