Description
Title: "Host Cell Tropism, Disease Tolerance and
Pathogen Avirulence”
Speaker: 
George S. Yap, Ph.D., M.S.
Professor,
Department of Medicine, Rutgers University
Abstract:
Immune resistance and disease tolerance are vital for mutual survivability of the host - parasite relationship. Virulence during Toxoplasma infection in mice is primarily mediated by parasite encoded kinase - dependent antagonism of IFN - γ - induced host resistance. Whether avirulence is a default status reflecting the absence of resistance - interfering factors or whether it requires expression of parasite factors that actively induce host tolerance mechanisms is not known. In exploring how avirulent and virulent strains of the parasite differentially interact with phagocytes, my laboratory has recently obtained evidence that avirulence in Toxoplasma requires parasite engagement of the scavenger receptor CD36. CD36 promotes macrophage tropism but is dispensable for the development of inn ate and adaptive immune resistance mechanisms. Instead CD36 is critical for re - establishing tissue homeostasis and survival following the acute phase of infection. Remarkably, the avirulence - associated CD36 - binding capacity of T. gondii is suppressed by th e virulence factor, ROP18, using a non - canonical kinase - independent mechanism. Thus, the absence of resistance - interfering virulence factors and the presence of tolerance - inducing avirulence factors are both required for long - term host - pathogen survival. I recently propose that successful parasites express avirulence determinants that actively induce disease tolerance pathways in the host to ensure mutual survivability of the host - pathogen relationship. Deciphering the nature of parasite avirulence factors and the corresponding disease tolerance/host resilience pathways they engage represents a new frontier for microbial pathogenesis research.
Bio:
George Yap obtained his BS and MS degrees from the University of the Philippines and his PhD
from McGill University in Montreal, under the supervision of Dr. Mary M. Stevenson. In 1994, he
joined the Immunobiology Section of the Laboratory of Parasitic Diseases, the National Institutes
of Allergy and Infectious Diseases of the NIH in Bethesda MD and worked under the supervision
of Dr. Allen Cheever and Dr. Alan Sher. At NIH, he dissected the roles of IL-12, IFN-gamma and
TNF-alpha in the host immune response to Toxoplasma gondii. This work led to an appreciation
for the role of IL-12 in the maintenance of Th1 immunity and for the role of iNOS-independent
mechanisms of cell-autonomous resistance of hemopoietic and parenchymal tissue cells to
intracellular parasitism. In 2000, Dr. Yap joined the Department of Molecular Microbiology and
Immunology at Brown University in Providence Rhode Island, where he taught immunology to
Brown undergraduates and established his independent research laboratory. His laboratory
discovered Tyk2 as a genetic determinant of disease susceptibility and identified a novel
mechanism for intracellular killing of the parasite Toxoplasma gondii. In 2007, Dr. Yap joined the
Center for Immunity and Inflammation at NJMS where he continues his research on T cell and
innate immune responses to Toxoplasma gondii. He has served as a Regular Member of Innate
Immunity and Inflammation Study Section of the NIH.
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.