Uncovering how age-associated inflammation alters the maturation and function of monocytes and macrophages and how these changes increase susceptibility to pneumonia

Accepting applications from post-doctoral fellows and graduate students.

Project Description:

The aging microenvironment is characterized by increased levels of circulating and tissue associated cytokines, broadly called “age-associated inflammation”. Very little is known about how this age-associated inflammation affects monocytes/macrophages but it appears as though there are changes that affect the very genesis of these cells and contribute to altered function with age and ultimately susceptibility to infections such as pneumonia.  By performing in vitro  and in vivo studies we are uncovering mechanisms by which macrophages from aged hosts are impaired. Because macrophages are involved in both infectious disease as well as homeostasis (e.g. tissue repair), we predict that understanding how macrophage function changes with age will have broad importance in both studies of infectious disease and chronic diseases that occur more frequently with age. Ultimately a better understanding of age-related changes in the immune response (immunosenescence) is essential to prevent infections such as pneumonia.

We have a number of projects ongoing in the lab;

  1. Using an aged mouse model of Streptococcus pneumoniae colonization and infection to uncover fundamental changes in the immune system that predispose to infection.
  2. Understanding how aging changes the genesis of myeloid cells and how this contributes to chronic inflammation and immune dysfunction.
  3. Investigating how elevated levels of inflammation contribute to changes in myeloid cell phenotype and function with age.

Team Members:
Post-doctoral fellows: Dr. Allison Kennedy
Graduate students: Anastasia Chouvalova
Undergraduate students:  Maiura Muralitharan

Collaborators:
Dr. Michael Rauh (Queen’s University)
Dr. Deborah Winter (Northwestern University)

Current Funding: CIHR

Previous Funding:OLA-Pfizer Research Award, CIHR catalyst grant

Alumni: Graduate students: Avee Naidoo (MSc), Alicja Puchta (PhD). Fan Fei (PhD), Dessi Loukov (PhD) Undergraduates: Danny Ma, Melodie Kiim, Samanthy Balachandran, Jessica Wallace, Dessi Loukov, Melissa Ling, Joseph Chong. Postdoctoral fellows: Dr. Christian Schulz

Publications (lab members marked in bold):

  1. Orihuela C, McElhaney J, Bowdish DME. Consequences of Pneumonia in Older Adults. In: Gu D, Dupre ME, eds. Encyclopedia of Gerontology and Population Aging. Cham: Springer International Publishing; 2019:1-8.
  2. Bowdish DME. The Aging Lung: Is lung health good health for older adults? Chest. 2018 Sep 22. pii: S0012-3692(18)32444-9. doi: 10.1016/j.chest.2018.09.003
  3. Lelic A, Verschoor CP, Lau VW, Parsons R, Evelegh C, Bowdish DM, Bramson JL, Loeb MB. Immunogenicity of Varicella Zoster Vaccine and Immunologic Predictors of Response in a Cohort of Elderly Nursing Home Residents. J Infect Dis. 2016 Oct 5. pii: jiw462
  4. Verschoor, CP., Lelic, A., Parsons, R., Evelegh, C., Bramson, JL., Johnstone, J., Loeb, MB, Bowdish, DME. Serum C-reactive protein and congestive heart failure are significant predictors of the varicella-zoster vaccine response in the nursing home elderly. J Infect Dis 2017 jix257. doi: 10.1093/infdis/jix25\
  5. Loukov D, Karampatos S, Maly MR, Bowdish DME. Monocyte activation is elevated in women with knee-osteoarthritis and associated with inflammation, BMI and pain. Osteoarthritis Cartilage. 2017 Nov 8. pii: S1063-4584(17)31300-6. doi: 10.1016/j.joca.2017.10.018.
  6. Verschoor CP, McEwen LM, Kobor MS, Loeb MB, Bowdish DME. DNA methylation patterns are related to co-morbidity status and circulating C-reactive protein levels in the nursing home elderly. Exp Gerontol. 2017 Oct 12. pii: S0531-5565(17)30513-2. doi: 10.1016/j.exger.2017.10.010.
  7. Kline KA, Bowdish DM. Infection in an aging population.Curr Opin Microbiol. 2015 Dec 10;29:63-67. doi: 10.1016/j.mib.2015.11.003.
  8. Verschoor CP, Loukov D, Naidoo A, Puchta A, Johnstone J, Millar J, Lelic A, Novakowski KE, Dorrington MG, Loeb M, Bramson JL, Bowdish DM. Circulating TNF and mitochondrial DNA are major determinants of neutrophil phenotype in the advanced-age, frail elderly.Mol Immunol. 2015 May;65(1):148-56. doi: 10.1016/j.molimm.2015.01.015.
  9. Puchta A, Verschoor CP, Thurn T, Bowdish DM. Characterization of inflammatory responses during intranasal colonization with Streptococcus pneumoniae. J Vis Exp. 2014 Jan 17;(83):e50490. doi: 10.3791/50490.
  10. Bowdish, D.M.E. Myeloid-derived suppressor cells, age and cancer. Oncoimmunology. 2:7, e24754; July 2013. Open access figure available for download.
  11. Dorrington, M.G., Bowdish, D.M.E. Immunosenescence and novel vaccination strategies for the elderly. 2013. Frontiers in Immunology.doi: 10.3389/fimmu.2013.00171 Media coverage: This paper was picked up by MDLinx. See their coverage here.
  12. Verschoor, C.P.,  Johnstone, J., Dorrington, M.G. Millar, J., Habibagahi, M., Lelic, A., Loeb, M., Bramson, JL.,  Bowdish, DME. Blood CD33(+)HLA-DR(-) myeloid-derived suppressor cells are increased with age, frailty and a previous history of cancer. 2013 J Leukoc Biol. 2013 Apr;93(4):633-7. doi: 10.1189/jlb.0912461. For supplementary data click here.
  13. Lelic A, Verschoor CP, Ventresca M, Parsons R, Evelegh C, Bowdish D., Betss, MR., Loeb, MB., Bramson, JL. (2012) The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age. PLoS Pathog 8(12): e1003076. doi:10.1371/journal.ppat.1003076

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