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.
Dr. Dawn Bowdish and her PhD student Dessi Loukov collaborated with Dr. Monica Maly and Sara Karampatos (Rehabilitation Science) and found that monocytes were more activated and pro-inflammatory in women with osteoarthritis, and that elevated inflammation and body mass index were associated with increased monocyte activation. Further, the team found that women with osteoarthritis and more activated monocytes experienced worse pain than individuals with less activated monocytes. These findings highlight the importance of modulating inflammation and body mass to manage osteoarthritis and open up new avenues for therapeutic research.
Read the full publication in the Osteoarthritis Research Society International (OARSI) Journal
As featured in Eureka Alert: https://www.eurekalert.org/pub_releases/2017-11/mu-rul112717.php
We’re thrilled that our publication was featured as an editorial in Cell Host & Microbe. Read Drs Erin S. Keebaugh and William W. Ja’s excellent editorial 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
Macrophages play a critical role in innate immunity by detecting, engulfing and destroying pathogenic bacteria and alerting neighbouring immune cells to join the fight against infection. They have many different receptors on their cell surface that allow them to carry out these important processes. A particular group of receptors called Scavenger Receptors are vital to this response. A recent study published in Immunology and Cell Biology by PhD student Kyle Novakowski from the laboratory of Dr. Dawn Bowdish has uncovered a mechanism by which a specific scavenger receptor contributes to macrophage-specific antibacterial immunity.
Scavenger Receptors are evolutionarily ancient and have evolved to recognize a wide array of pathogens by detecting ligands that are common across many pathogenic organisms. A particularly important Scavenger Receptor is Macrophage Receptor with Collagenous Structure, or MARCO. MARCO has been shown to significantly contribute to the clearance of Streptococcus pneumoniae colonization of the nose and in models of pneumococcal pneumonia. The NSERC-funded study took a unique approach to functionally characterizing how MARCO contributes to innate immunity by studying a naturally-occurring variant of the receptor. The study highlighted the importance of a particular domain of the receptor that is required for macrophages to bind and internalize ligands. The study also showed that the domain is necessary to enhance the pro-inflammatory response to pathogenic Streptococcus pneumoniae and can enhance cellular adhesion; both vital to proper macrophage functions.
To read the article, please click here.