‘Inflamm-aging’ by seniors may impact pneumonia susceptibility

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.

Funding from the province of Ontario supports two new graduate students!

Bowdish lab receives funding from the province of  Ontario to train two new graduate students! Avee Naidoo (MSc) and Dessi Loukov, who will be starting a PhD in Sept 2013,  will be studying how age-associated inflammation predisposes older adults to pneumonia.

For full details on the award for Dawn’s proposal “Interplay between inflammation and impaired anti-bacterial immunity in the elderly.”

Dessi Loukov, pictured here pushing back the boundaries of science.

Dessi Loukov, pictured here pushing back the boundaries of science.

Aveshni Naidoo, MSc sits beside the coolest jack-o'-lantern ever.

Aveshni Naidoo, MSc sits beside the coolest jack-o’-lantern ever.

“Myeloid-Derived Suppressor Cells, Age & Cancer” 2013. Oncoimmunology.

Dr. Bowdish discusses the implication of our Verschoor et al publication “Blood CD33(+)HLA-DR(-) myeloid-derived suppressor cells are increased with age and a history of cancer.” in studies of aging and cancer in the below commentary.

Click image for .pdf.

MDSC commentary


This is an open access publication so please feel free to use the following image in presentations/publications providing that it is properly referenced.

MDSC commen figure

“Immunosenescence & novel vaccination strategies for the elderly” 2013. Dorrington et al. Frontiers in Immunology

What is the best way to reduce infectious disease in the elderly? Vaccination! Unfortunately the aging immune system presents a number of challenges for vaccine development. Bowdish lab PhD candidate Mike Dorrington discusses them in this review and presents a case for developing novel vaccines that work within the constraints of the aging immune system.

Media coverage: This paper was picked up by MDLinx. See their coverage here.

Click image for .pdf.

Dorrington Fronteirs review

“Blood CD33+HLA-DR- myeloid-derived suppressor cells are increased with age and a history of cancer” 2013. Verschoor et al. JLB

MDSCs (myeloid derived suppressor cells) are a recently discovered and very heterogenous cell type that appear to directly suppress T cell responses and their presence in the tumour or the circulation is an extremely poor prognostic marker.

The Bowdish lab recently dipped our foot into the confusing world of MDSCs because we were curious to know whether their frequency increases with age and if so, could this explain why age is a risk factor for many cancers. They do increase with age and this may explain why some adaptive immune responses decline with age. One thing we were very surprised to find is that individuals who had any history of cancer but were believed to be in remission had higher levels of these cells in circulation. This begs the question – did these people have higher levels and to begin with and is this why they were predisposed to cancer? Or do they still have subclinical tumours that promote the development of MDSCs? Or does the suppressive environment of the cancer microenvironment stay with you for life? More studies (not by us, that was enough) are warranted.

For the .pdf click here

For the supplementary data, click here.

Grant Bonanza!

The Bowdish lab has received funding from the CIHR (Pilot Projects in Aging) with Dr. Jennie Johnstone to study how macrophage immunosenescence contributes to susceptibility to pneumonia in the elderly. We have also received funding from the Ontario Thoracic Society/Ontario Lung Association for our work on the role of scavenger receptors in mycobacterial infection and funding from the CIHR (Emerging Team: Human Microbiome, with Drs Mike Surette, Jennie Johnstone, Mike Schryvers, & James Kellner) to study the role of commensal bacteria (including close cousins of S. pneumoniae) contribute to upper respiratory tract infections. This is truly an exciting time for the Bowdish lab – stay tuned for some fantastic science!

(Position filled Sept 14 2010) Post-doctoral position in Immunosenescence Available

Would you like to build your career exploring the immunology of aging?

In the Western world the majority (>90%) of deaths due to pneumonia occur in the elderly. Why they are at such high risk is not entirely clear, but presumably immunosenescence (age related changes in the immune system) is a key factor.  The high mortality rate is compounded by co-infections, such as influenza infection. This research project involves developing a mouse model of Streptococcus pneumoniae colonization and infection in aged mouse and determining how co-infection with influenza increases the risk of developing pneumonia. This will include a both a basic science component (i.e. deteremining how age-associated changes in immunity contribute to susceptibility to infection) and a translational component (i.e. testing therapeutic interventions).

An immediate post-doctoral opportunity is available for a creative scientist with a strong commitment to excellence and innovation to pursue leading edge research in immunology. Although this is presently only a 1 year position, this may be extended if the applicant obtains fellowship funding. Candidates with experience in virology or mouse models of infection are especially encouraged to apply.

The position is in the Department of Pathology & Molecular Medicine at McMaster University located in the heart of the Golden Horseshoe in southern Ontario.  McMaster University has been ranked as one of Canada’s most research intensive universities known for it’s highly collaborative and mentoring atmosphere.

Interested candidates should send a CV, cover letter and three references to Dr. Dawn Bowdish (bowdish@mcmaster.ca, www.bowdish.ca).