Understanding how age-associated changes in innate immunity increase susceptibility to infection

Accepting applications from post-doctoral fellows with independent funding. All graduate positions are filled until Sept 2017. 

Project Description:

Macrophage receptor expression is dynamic and depends on factors in the local environment (e.g. the cytokine milieu, cell-cell interactions, exposure to pathogen associated molecular patterns). 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 infectious disease.  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 design adjuvants and immunomodulatory agents that this population so urgently requires. 

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 may contribute to chronic inflammatory diseases.
  3. Investigating how elevated levels of inflammation contribute to changes in myeloid cell phenotype and function with age.

Team Members:

Post-doctoral fellows: Dr. Christian Schulz

Graduate students: Dessi Loukov (PhD candidate)

Undergraduate students:  Joseph Chong

Collaborators:

  • Drs Jonathan Bramson, Mark Loeb & Jennie Johnstone (studies on changes in myeloid cell phenotype and function in the elderly)
  • Dr. Param Nair (studies of S. pneumoniae interactions with macrophages of the upper respiratory tract)

Current Funding: CIHR,

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

Alumni: Graduate students: Avee Naidoo (MSc), Alicja Puchta (PhD). Fan Fei (PhD) Undergraduates: Samanthy Balachandran, Jessica Wallace, Dessi Loukov, Melissa Ling

Publications (lab members marked in bold):

  1. 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.
  2. 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.
  3. Puchta A, Verschoor CP, Thurn T, Bowdish DMCharacterization of inflammatory responses during intranasal colonization with Streptococcus pneumoniae. J Vis Exp. 2014 Jan 17;(83):e50490. doi: 10.3791/50490.
  4. Bowdish, D.M.E. Myeloid-derived suppressor cells, age and cancer. Oncoimmunology. 2:7, e24754; July 2013. Open access figure available for download.
  5. 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.
  6. 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.
  7. 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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