Education and Professional Standing
PDF. University of Oxford, 2008
PhD. University of British Columbia, 2005
BSc. University of Guelph, 2000
Macrophages are the sentinel cells of the immune response; their role is to detect pathogens via expression of surface receptors. Generally they are effective in clearing the pathogen without mounting an inflammatory response; however, when a pathogen evades detection or clearance, they are instrumental in mobilizing an appropriate immune response. In some cases a frustrated attempt to resolve infection or an inappropriate response to non-infectious stimuli can result in tissue damage and sterile inflammation. Because macrophage receptors are crucial to this initial interaction to pathogens and shape the downstream immune response, factors that alter the rate or magnitude of receptor expression (e.g. slight genetic variations in receptor genes) can have profound effects on an individual’s susceptibility to infection.
- The role of the macrophage scavenger receptors in host defence
The two major class A scavenger receptors are called SRA (scavenger receptor, class A) and MARCO (macrophage receptor with collagenous structure), which have high levels of homology but sharply opposing patterns of regulation. SRA is constitutively expressed on macrophages whereas MARCO expression is inducible and is upregulated in response to toll like receptor agonists. The primary role of SRA appears to be clearance of modified host proteins and lipids while MARCO is associated with the response to infectious disease. Mice defective in expression of either MARCO or SRA are immunocompromised in multiple models of infection. Preliminary data indicates that these receptors may be especially important in host defence towards the pulmonary pathogens Streptococcus pneumoniae and Mycobacterium tuberculosis. Ongoing work is being performed to determine the role of these receptors in binding, recognition and signalling in response to bacterial components and recruitment and motility of leukocytes.
- Understanding the complex interplay between commensals and resident pathogens in the upper respiratory tract
Very little is known about the macrophages and antigen presenting cells of the upper respiratory tract interact with commensals and resident pathogens of the upper respiratory tract, or indeed even the composition of the microflora of the upper respiratory tract. Our work involves characterizing recognition and responses to colonization and infection in the upper respiratory tract and immunophenotyping the resident and recruited cells to the upper respiratory tract.
- Discovering age-associated changes in innate immunity that correlate with susceptibility to infection
Macrophage receptor expression is dynamic and depends on factors in the localenvironment (eg: the cytokine milieu, cell-cell interactions, exposure to pathogen associated molecular patterns) and change with age. Very little is known about how monocyte/macrophage functions change as we age and how this predisposes us to disease. We aim to determine, on the populatione level, whether age associated changes in moncyte/macrophage receptor expression and function contribute to susceptibility of the elderly to infectious disease. Manipulation of expression is useful in design of adjuvants and immunomodulatory agents that this population so urgently requires.
Visit Dr Bowdish's McMaster Immunology Research Centre (MIRC) web profile for more information