Description
Title: "Innate immunity to liver-stage malaria”
Speaker:
Samarchith Kurup, DVM, PhD
Assistant Professor, Department of Cellular Biology
University of Georgia
Abstract:
Plasmodium parasites undergo mandatory development and replication in hepatocytes before initiating the life-threatening blood-stage malaria. The innate immune responses generated against Plasmodium in the liver are key to impeding clinical malaria and transmission. We show that Plasmodium DNA is sensed by AIM2 (absent in melanoma 2) receptors in the infected hepatocytes, leading to inflammasome mediated Caspase-1 activation, and pyroptotic cell-death. Remarkably, and in contrast to in the well-studied myeloid cells, Caspase-1 undergoes only partial cleavage in the hepatocytes, limiting pyroptosis, and the maturation of pro-inflammatory cytokines. We demonstrate that the expression of ASC (apoptosis-associated speck-like protein containing a CARD) determines the extent of Caspase-1 cleavage in cells, and is inherently low in hepatocytes. Transgenically enhancing ASC in hepatocytes induced complete processing of Caspase-1, efficient secretion of pro-inflammatory cytokines, enhanced pyroptotic cell-death, and markedly improved control of malaria in the liver. We here uncover a new pathway of natural immunity to malaria, and a key piece of liver biology perhaps pertinent to all diseases of the liver.
Bio:
Sam earned his degree in veterinary medicine from the Kerala Agricultural University in India and his Masters degree in parasitology from the Indian Veterinary Research Institute. He then moved to the United States, to do his PhD in Cellular Biology at the University of Georgia, where he studied the immunology of Trypanosoma cruzi with Dr. Rick Tarleton. Sam later went to the University of Iowa for his postdoctoral training with Dr. John Harty, where he found his passion of studying host immune responses in malaria. Sam established his own research group at the University of Georgia's Center for Tropical and Emerging Global Disease in 2019, where he continues the research on malaria immunology.
Date: Monday, May 8, 2023
Time: 12-1 pm
Location: Hill 132 or Virtually Via Zoom
Questions? Please contact Michael Black if you have questions.