The Loke Lab studies the type-2 immune responses against different inflammatory conditions. One response we study is specifically looking at parasitic worms, or helminths. We want to understand the mechanisms that helminths and macrophages use to regulate our immune responses. Helminth infections are neglected diseases that cause enormous morbidity to populations predominantly in the developing world. However, they may also have properties that can prevent autoimmune diseases. Macrophages are ancient and important cells that regulate many aspects of mammalian physiology and are vital for host defense.
Helminths induce a population of macrophages that are dependent on type 2 cytokines (IL-4 and IL-13), also called alternatively activated M2 macrophages. M2 macrophages are critical for enabling the host to tolerate and resist helminth infections. We are characterizing the origin and functional properties of M2 macrophages during infection, as well as other inflammatory diseases, using a combination of intra-vital microscopy, cellular immunology and new strains of reporter mice. We have also been studying how gastrointestinal helminths may regulate intestinal immune responses and interact with the gut microbiota. We characterized the response of an individual who self-infected with helminths to treat his symptoms of ulcerative colitis in order to better understand how helminths could suppress inflammatory bowel diseases. We use mouse models, clinical trials and field studies in Malaysia to determine how helminths, the gut microbiota and intestinal immune responses interact.
Using what we have learned from studying helminths, we wanted to apply this knowledge to another inflammatory disease; atherosclerosis. Atherosclerosis is a leading cause of death worldwide but many of the disease mechanisms are still unknown. Using our mouse models of reporter mice, we are interested in the way M2 macrophages interact with other immune cell types within the heart plaque. We are hopeful that a better understanding of these populations can lead to a more targeted approach to disease regression.