Dissecting the complex interplay between host immune cells and the microbiota of the upper respiratory tract

Applications from post-doctoral fellows with independent funding will be considered. There are currently no graduate student positions for this project. 

Project Description

Very little is known about the composition of the immune cells of the upper respiratory tract. For example, we and others have isolated resident macrophages and antigen presenting cells from the upper lungs (via sputum samples) and sinuses (via nasal washes) but even these two populations have very different phenotypes and likely functions. Presumably these cells are required for control of resident pathogens and may even promote the growth of  commensal organisms (even such a thing truly exists in the upper respiratory tract!) but how this host-microbe interactions occur are unclear. In fact even the composition of the microbiome of the upper respiratory tract in health, illness and age is not  well defined. Our work involves characterizing the composition of the microbiome of the upper respiratory tract, especially in the context of age, uncovering mechanisms of macrophage-mediated recognition of commensals and pathogens and immunophenotyping the resident and recruited myeloid cells. The gateway of debilitating infections such as pneumonia and influenza is the upper respiratory tract and understanding how how defence works and why it fails is a pre-requisite to discovering novel immunotherapeutics.

We have a number of ongoing projects in the lab:

  1. Understanding host-pathogen interactions between the Streptococcus milleri group, a family of resident pathogens of the upper airways, and monocytes/macrophages and epithelial cells. (with Dr. Mike Surette)
  2. Developing mouse models of invasive disease by the Streptococcus milleri group (with Dr. Mike Surette).
  3. Characterizing changes in the microbiome of the upper respiratory tract with age and during the course of colonization with Streptococcus pneumoniae. (with Dr. Mike Surette)
  4. Testing the ability of probiotics to prevent upper respiratory tract infections in the elderly (with Dr. Mark Loeb and Dr. Mike Surette)

Team Members

Graduate Students: Netusha Thevaranjan (MSc student), Pat Schenck (PhD student, co-supervised by Mike Surette & Dawn Bowdish), Karissa Giraldi (MSc candidate, supervised by Dr. Mike Surette, collaborates with the Bowdish lab), Michelle Mendoca (PhD candidate, supervised by Dr. Mike Surette, collaborates with the Bowdish lab)

Collaborators:

  • Dr. Mike Surette (obviously!)
  • Dr. Param Nair (characterization of sputum and sinus leukocyte populations during health and disease)
  • Drs. Mark Loeb, Jennie Johnstone, Jonathan Bramson, Deborah Cook (probiotics for immunomodulation and prevention of infection in the elderly).

Current Funding: CIHR (Emerging Team: Human Microbiome), Labarge Optimal Aging Initiative

Alumni: Dr. Jennifer Stearns,(PDF  with Dr. Mike Surette) Dr. Peter Pelka (PDF), Dr. Preethi Jayanth (PDF co-supervised with Dr. Mike Surette),Julie Kaiser (MSc, co-supervised with Dr. Mike Surette), Netusha Thevaranjan (undergraduate).

Publications (lab members marked in bold):

  1. Johnstone J, Meade M, Marshall J, Heyland DK, Surette M, Bowdish D, Lauzier F, Thabane L, Cook DJ. Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial: PROSPECT: Protocol for A Feasibility Randomized Pilot Trial. Pilot and Feasibility Studies 2015; 1:19.
  2. Stearns JC, Davidson CJ, McKeon S, Whelan FJ, Fontes ME, Schryvers AB, Bowdish DM, Kellner JD, Surette MG. Culture and molecular-based profiles show shifts in bacterial communities of the upper respiratory tract that occur with age. ISME J. 2015 May;9(5):1268. doi: 10.1038/ismej.2015.49.
  3. Verschoor CP, Dorrington MG, Novakowski KE, Kaiser J, Radford K, Nair P, Anipindi V, Kaushic C, Surette MG, Bowdish DME. MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx.Infect Immun. 2014 Nov;82(11):4824-33. doi: 10.1128/IAI.02251-14.This paper outlines how microRNA- (miR-)155 regulates the immune response to S. pneumoniae colonization in the nasal passages of mice by stimulating the differentiation of Th17 cells. 
  4. Kaiser JC, Verschoor CP, Surette MG, Bowdish DME. Host cytokine responses distinguish invasive from airway isolates of the Streptococcus milleri/anginosis group. BMC Infect Dis. 2014 Sep 11;14:498. doi: 10.1186/1471-2334-14-498.This paper demonstrates that there are host- and strain- specific responses to isolates of the Streptococcus milleri/anginosis group and that isolates from invasive disease appear to be more immunostimulatory than those from commensal relationships.
  5. Whelan FJ, Verschoor CP, Stearns JC, Rossi L, Luinstra K, Loeb M, Smieja M, Johnstone J, Surette MG, Bowdish DM. The Loss of Topography in the Microbial Communities of the Upper Respiratory Tract in the Elderly. Ann Am Thorac Soc. 2014 Mar 6.This paper describes how the microbial communities of the anterior nares and nasopharynx change between adults and the elderly. 

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