Presentation day

Thursday  3:30 PM

 

TITLE

Innate immunity peptides and self-assembly

 

Abstract

Host defense peptides (HDP) have a broad range of functions, from permeating bacterial
membranes to modulation of adaptive immunity. We show how host defense peptides drive self-assembly
processes that achieve these outcomes. By combining coordination chemistry with topology, we show how
HDP can self-assemble with membranes and permeate them in a selective manner. Moreover, we examine
how immuno-modulatory activity can be multiplexed into these same sequences: Double-stranded DNA
(dsDNA) can trigger type I interferon (IFN) production in plasmacytoid dendritic cells (pDCs) by binding to
endosomal Toll-like receptor-9 (TLR9). We demonstrate how self-assembly between HDP and DNA can
lead to nanostructured particles that can activate the adaptive immune system via TLR9, and elucidate the
criterion for TLR9 activation by combining synchrotron x-ray scattering, computer simulations, and direct
measurements of pDC IFN production.