PhD student Dessi Loukov in the lab of Dr. Dawn Bowdish, recently published a study showing that splenomegaly in old mice is a result of extramedullary hematopoiesis, and that this increased monopoiesis is driven by age-associated increase in TNF. The study compared changes in the microarchitecture and composition of the spleen in old and young mice and found that in old mice, there was an increase in the size and cellularity of the red pulp (the site of hematopoiesis of myeloid precursors). To study the role of TNF in the development of extramedullary hematopoiesis, they used TNF KO mice and found that these mice did not have increased extramedullary monopoiesis. Furthermore, they demonstrated that increased splenic myelopoiesis was a result of the aging microenvironment. This work suggests that strategies which aim to decrease the inflammatory microenvironment that comes with aging, would be effective in reducing inflammatory diseases propagated by cells of the myeloid lineage. Read More
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.
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.
Aveshni Naidoo, MSc sits beside the coolest jack-o’-lantern ever.
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.
This is an open access publication so please feel free to use the following image in presentations/publications providing that it is properly referenced.
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.
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.
Dawn will be presenting a talk entitled “Immunosenescent macrophages cannot control Streptococcus pneumoniae colonization” 9:45 am Oct 7th and poster entitled the same at 11-12 Oct 8th. For the rest of the program click here.