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. Understanding how age-related increases in the the cytokine TNF changes the genesis of myeloid cells,  and impairs myeloid and macrophage function.
2. Understanding sex differences in age-associated inflammation and function.

Team Members:
Post-doctoral fellows: Dr. Kemy Ade
Graduate students: Kevin Zhao (MD/PhD candidate), Sofya Ermolina (PhD candidate)
Undergraduate students:  Molly Health, Aunika Venables

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

Current Funding: NSERC Discovery Grant

Alumni: Graduate students: Ana Chouvalov (MSc), 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, Dr. Allison Kennedy, Dr. Candice Quin

Publications (lab members marked in bold):

1. Kelagere Y, Scholand KK, DeJong EN, Boyd AI, Yu Z, Astley RA, Callegan MC, Bowdish DM, Makarenkova HP, de Paiva CS. TNF is a critical cytokine in age-related dry eye disease. Ocul Surf. 2023 Oct;30:119-128. doi: 10.1016/j.jtos.2023.08.004.
2. Breznik JA, Foley KP, Maddiboina D, Schertzer JD, Sloboda DM, Bowdish DME. Effects of Obesity-Associated Chronic Inflammation on Peripheral Blood Immunophenotype Are Not Mediated by TNF in Female C57BL/6J Mice. Immunohorizons. 2021 Jun 4;5(6):370-383. doi: 10.4049/immunohorizons.2100038.
3. Breznik JA, Schulz C, Ma J, Sloboda DM, Bowdish DME. Biological sex, not reproductive cycle, influences peripheral blood immune cell prevalence in mice. J Physiol. 2021 Apr;599(8):2169-2195. doi: 10.1113/JP280637. Epub 2021 Jan 17. PMID: 33458827.
4. 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.
5. 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
6. 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
7. 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\
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Bowdish, D.M.E. Myeloid-derived suppressor cells, age and cancer. Oncoimmunology. 2:7, e24754; July 2013. Open access figure available for download.
14. 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.
15. 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.
16. 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