2017 SCEP Symposium Archive
New York University
"Regulation of intestinal inflammation by helminths and the microbiota"
The Loke Lab studies the type-2 immune response against 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.
- Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
Girgis NM, Gundra UM, Ward LN, Cabrera M, Frevert U, Loke P.
PLoS Pathog. 2014 Jun 26;10(6):e1004080. doi: 10.1371/journal.ppat.1004080. eCollection 2014 Jun.
- Helminth colonization is associated with increased diversity of the gut microbiota.
Lee SC, Tang MS, Lim YA, Choy SH, Kurtz ZD, Cox LM, Gundra UM, Cho I, Bonneau R, Blaser MJ, Chua KH, Loke P.
PLoS Negl Trop Dis. 2014 May 22;8(5):e2880. doi: 10.1371/journal.pntd.0002880. eCollection 2014 May.
- Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct.
Gundra UM, Girgis NM, Ruckerl DA, Jenkins S, Ward LN, Kurtz ZD, Wiens KE, Basu-Roy U, Mansukhani A, Allen JE, Loke P.
Blood (In Press).
- Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences.
Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, Kim SG, Li H, Gao Z, Mahana D, Zárate Rodriguez JG, Rogers AB, Robine N, Loke P, Blaser MJ.
Cell. 2014 Aug 14;158(4):705-21. doi: 10.1016/j.cell.2014.05.052.