Tag Archives: Streptococcus pneumoniae

Publication: Neutrophil-mediated innate immune resistance to bacterial pneumonia is dependent on Tet2 function

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https://bsky.app/profile/msmacrophage.bsky.social/post/3kubwknbcts2e
Click here for the full thread from Bluesky highlighting the major findings of the paper.
To see the full paper click here:
To see the commentary click here:



Bluesky thread:

Let me tell you about the #BowdishLab & friend’s most recent paper “Neutrophil-mediated innate immune resistance to bacterial pneumonia is dependent on Tet2 function”, led by Dr. C. Quin (now at @uniofaberdeen.bsky.social) @jclinical-invest.bsky.social https://www.jci.org/articles/view/171002
Tet2 is gene that is involved with methylating genes and therefore changing gene expression. Sometimes spontaneous mutations of Tet2 in hematopoetic stem cells (HSC) occur. These mutants tend to produce more myeloid cells (monocytes/neutrophils).
These myeloid producing HSCs tend to be more fit in the aging bone marrow (Darwinian survival of the fittest) and overtime, more and more of your myeloid cells are made from these Tet2 mutant clones.
In extreme cases this can lead to myelodysplastic disorders or cancer, but sub-clinical CHIP or clonal hematopoeisis of indeterminant potential occurs in many older adults.
People with CHIP (i.e., too many of their myeloid cells are made from Tet2 mutant progenitors) are prone to all sorts of conditions (e.g., heart disease) and pneumonia. We hypothesized that pneumonia risk might be due to changes in innate immune/myeloid cell function.
Mice defective in Tet2 did very poorly during Streptococcus pneumoniae infection (the most common cause of community acquired pneumonia in older adults), because their neutrophils were less able to kill bacteria.
We are excited about this @jclinical-invest.bsky.social publication because it is the first mechanistic explanation for the increased risk of pneumonia in CHIP. Generally CHIP is thought to affect macrophage function, but it clearly affects neutrophil gene expression & function as well.
Many thanks to Dr. Elsa Bou Ghahem for her most excellent Commentary https://www.jci.org/articles/view/181064 and for the great editorial & reviewer experience @jclinical-invest.bsky.social
Research Team:Candice Quin, Erica N. DeJong, Elina K. Cook, Yi Zhen Luo, Caitlyn Vlasschaert, Sanathan Sadh, Amy J.M. McNaughton, Marco M. Buttigieg, Jessica A. Breznik, Allison E. Kennedy, Kevin Zhao, Jeffrey Mewburn, Kimberly J. Dunham-Snary, Charles C.T. Hindmarch, Alexander G. Bick, Stephen L. Archer, Michael J. Rauh, Dawn M.E. Bowdish

Congratulations to Pat Schenck & Jessica Breznik on winning the Farncombe Research in Progress Awards!

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Jessica Breznik (co-supervised by Dr. Deborah Sloboda) won the “Best Presentation by a PhD student” while Pat Schenck (co-supervised by Dr. Mike Surette) won runner up!  What a wonderful tribute to their skills in both research and communication – well done!

Kyle Novakowski is the Bowdish lab’s newest PhD!

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Kyle Novakowski successfully defended his thesis “IDENTIFICATION AND  FUNCTIONAL CHARACTERIZATION OF CONSERVED RESIDUES AND DOMAINS IN THE MACROPHAGE SCAVENGER RECEPTOR MARCO”  to become the Bowdish lab’s 4th PhD student. He’ll be joining Turnstone Biologics as a PhD scientist. We wish him very well in his future endeavours. Congratulations Dr. Novakowski!

Publication: Streptococcus pneumoniae Colonization Disrupts the Microbial Community within the Upper Respiratory Tract of Aging Mice

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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 howNetusha-sm 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

‘Inflamm-aging’ by seniors may impact pneumonia susceptibility

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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.