10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
Abstract View
Host Transcriptomic Responses Predict Disease Severity in Nonhuman Primates Exposed to Small or Large Particle Aerosols Containing Burkholderia pseudomallei
JEREMY BOYDSTON, Adrian Caciula, Paul Dabisch, Xiaoyu Che, John Yeager, Jill Taylor, Gregory Williams, Ian Lipkin, Michael Hevey, Angela Rasmussen, BNBI / DHS NBACC
Abstract Number: 517 Working Group: Infectious Bioaerosol
Abstract Burkholderia pseudomallei is a gram negative bacteria found in soil and water in Australia and Southeast Asia. Environmental exposure to B. pseudomallei, which may occur via percutaneous or inhalational exposure, results in the disease melioidosis. While the particle size distribution of naturally occurring aerosols containing B. pseudomallei has not been measured, measurements of naturally occurring aerosols containing other microorganisms suggest a wide range of particle sizes are possible. For many microorganisms, there is evidence that aerodynamic particle size is a significant factor influencing the disease presentation and lethality. Therefore, the aim of the present study was to examine the influence of aerodynamic particle size on the host transcriptional response to inhalational exposure of B. pseudomallei in nonhuman primates (NHPs). RNA-seq analysis of a time-series of blood samples revealed similar differential expression profiles independent of aerodynamic particle size. However, gene expression signatures were detected early in infection that allowed differentiation between NHPs that developed mild disease and those that developed severe or lethal disease. For example, activation of T-cells, specifically the T-helper 1 activation pathway involved in cell mediated immunity and macrophage activation, was significantly downregulated in NHPs that developed severe melioidosis, but not in those that developed mild disease. Such differences may be useful in the development of new prognostic assays. Transcriptomic signatures were also used to identify licensed drugs that are predicted to inhibit the expression profiles observed with severe disease, providing potential therapeutic candidates for future evaluation.
This work was funded under Contract No. HSHQDC-15-C-00064 awarded by the Department of Homeland Security (DHS) Science and Technology Directorate (S&T) for the operation and management of the National Biodefense Analysis and Countermeasures Center (NBACC), a Federally Funded Research and Development Center. The views and conclusions contained in this document are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of the DHS or S&T. In no event shall DHS, NBACC, S&T or Battelle National Biodefense Institute have any responsibility or liability for any use, misuse, inability to use, or reliance upon the information contained herein. DHS does not endorse any products or commercial services mentioned in this publication.
All research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals (National Research Council, 2011). The facility where this research was conducted is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International.