‘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.

Novemer 12th is World Pneumonia Day – celebrate by getting vaccinated against influenza and pneumococcal pneumonia!

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:

http://www.cbc.ca/news/canada/toronto/programs/metromorning/researchers-find-getting-the-flu-can-lead-to-other-diseases-1.3315848

Read about why older adults should be vaccinated against pneumococcal pneumonia and influenza, as profiled by the CBC here:
http://www.cbc.ca/news/health/flu-vaccines-mcmaster-1.3315511?cmp=rss

and here

http://www.cbc.ca/news/canada/toronto/programs/metromorning/pathologist-deeply-saddened-vaccines-distrust-1.3315893

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:
http://www.am980.ca/the-pulse/

To read about the link between dementia and pneumonia:
http://www.atsjournals.org/doi/abs/10.1164/rccm.201212-2154OC#.VkTWTHarRaR

To read about the link between cardiovascular disease and pneumonia
http://jama.jamanetwork.com/article.aspx?articleid=2091304

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.

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.

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.

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.

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.”
http://iidr.mcmaster.ca/IIDR-news/ERAs-2014.html#.UzXGj_ldWSo

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.

“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