Phagocyte biology laboratory
Welcome! You have reached the homepage for the laboratory of Dr. Bryan Heit. Our lab is part of the Department of Microbiology and Immunology at Western University, and we are members of the Center for Human Immunology, the lead centre for the CIHR Human Immunology Network.
Our interests surround the function of phagocytes – white blood cells which ingest (phagocytose) pathogens, particles, and dead cells. We focus on the cellular and molecular processes which control the function of these cells during the maintenance of homeostasis, infection and chronic inflammatory disease. Central to most of our studies is the study of efferoctyosis – the phagocytic removal of apoptotic (dying) cells, and how failures in this process lead to inflammation, autoimmunity and infection.
What is a Phagocyte?
Phagocytes are a class of white blood cells which have the capacity to engulf large particles such as bacterial and fungal pathogens, and subsequently destroy the engulfed material. The term phagocyte literally translates to “cell that eats”, which is an apt description of the primary function of these cells in our bodies. While there are many types of phagocytes, the Heit lab focuses primarily on macrophages, which play key roles in both maintaining our bodies and in fighting infections.
We use a combination of advanced microscopy techniques, gene expression analysis and functional assays to investigate the activity of macrophages. Some examples of the methods we employ can be found on our YouTube channel.
COVID-19 and Adaptive Immunity
We are excited to announce our second COVID-19 publication. This review provides an up-to-date summary of what is known of how SARS-CoV-2 interacts with, and manipulates, the adaptive immune system. This includes a detailed assessment of how SARS-CoV-2 manipulates antibody responses, and how these responses then relate to viral clearance.
This review includes discussion of how these mechanisms may affect the efficacy of vaccines and immunotherapies directed against this virus, and investigates the potential of novel appearances to immune modulation to help support the adaptive immune system as it fights this potent pathogen.
This review is published in Pathogens.
GATA2 and the Onset of Atherosclerosis
We are excited to announce the publication of our research into the events which initiate atherosclerosis. Atherosclerosis is why we worry about cholesterol in our diets, and is one of the leading causes of death globally. Atherosclerosis is driven by the formation of “plaques” – masses of dead, cholesterol-filled macrophages in the blood vessels of the heart. These plaques can rupture, causing a heart attack or stroke. The processes that start this disease are poorly understood. Our new study – published in Frontiers in Immunology – begins to uncover these early events. We have discovered that pre-plaque macrophages loose expression of the genes which would allow for them to remove and process dying cells – a critical step in preventing plaque formation. This loss of “efferocytosis” (dead cell clearance) sets the stage for the accumulation of dead cells that form the plaque.
The key discovery in this study was the identification of the transcription factor GATA2 as the “mater regulator” of this lost efferocytosis ability. GATA2 controls the expression of other genes, and in these patients’ macrophages, GATA2 turns off many of the genes needed to recognize, engulf and destroy dead and dying cells. In the future, treatments targeting GATA2, or the pathways which activate GATA2, may serve as therapies for preventing or reversing atherosclerosis. This study would not have been possible without the amazing work of our collaborator Dr. David Nagpal of the London Health Sciences Centre, and funding from the Heart and Stroke Foundation of Canada.
COVID-19: Innate Immunity Review
The Heit lab is excited our first piece of COVID-19 work – a detailed review on the interactions of the SARS-CoV-2 virus with the innate immune system. COVID-19 has a plethora of mechanisms to avoid being detected and cleared by the innate immune system, and as such, undergoes highly complex interactions with the innate immune system. This review has been published in Frontiers in Immunology.
November 2020 Update: This article has been read more than 67,000 times – making it one of the most-read articles in 2020 across all of Frontier’s journals!
December 2020 Update: The University of Toronto’s IMM340 course has interviewed the lead author of this paper, and incorporated this interview into a video on COVID-19 research.
Rab GTPase Review
Much of the research in the Heit lab focuses on the role of Rab GTPases in regulating the activity of immune cells. Rab GTPases are the master controllers of vesicular trafficking – the cellular system which lets “packages” of materials be delivered to specific location in the cell. In this review we go in-depth into the role of Rab GTPases in allowing immune cells to engulf and degrade both pathogens and innocuous cell debris – and how Rab GTPases then allow the immune cell to mount an immune response to to former, but not the latter.
This invited review is published in Histology and Histopathology.