Myeloid-Derived Suppressor Cells in Aged Humans
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells whose
immunosuppressive activities contribute to cancer and other diseases. MDSCs
appear to increase with age, and this presumably contributes to immunosuppression
and the increased incidence of certain diseases. Why MDSCs increase with
age is not entirely clear. Herein we present evidence that MDSC expansion is due
in part to age-related changes in hematopoiesis, including the acquisition of
mutations that favor myelopoiesis, which are compounded by changes in the
aging microenvironment that favor the production of MDSCs.
Congratulations to the newly minted Dr. Loukov on successfully defending her thesis entitled “Age-Associated Inflammation impairs Myeloid Development and Monocyte & Macrophage Function”!
The newly minted Dr. Loukov drinks from the chalice.
Dessi celebrates her thesis defence with one of her mentors Dr. Mark McDermott.
The Bowdish lab was very proud to host Anika Gupta, a high school student, for her Bay Area Science and Engineering Fair (BASEF) project.
Her project was entitled “Quantifying Lung Macrophages to Understand Increased Susceptibility to Bacterial Pneumonia with Age.”
Anita won the Dr. Doyle Biology Award for the best Biology project, a Gold merit award as well as the Pinnacle Award for the Third Best in Fair and a sponsored Trip Award to compete in the Intel International Science and Engineering Fair in Pittsburgh, Pennsylvania in May!
Way to go Anika!
Anika Gupta receiving the third place “ArcelorMittal Dofasco Pinnacle Best-in-Fair” award.
See her featured in the Hamilton news here.…
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.