Macrophages are key cells that direct innate immune responses to pathogens that are detected through specific pattern recognition receptors. We will analyze the transcriptomes of macrophages infected with Burkholderia pseudomallei and determine the transcription factors and signaling molecules that are activated in response to infection. By examining macrophages deficient for central signaling molecules, we will ascribe specific transcriptional clusters to TLR signaling (MyD88/Trif null cells), NLR signaling (Rip2 or caspase 1 null cells) or type I interferon signaling (IFNaRI null cells). In parallel, we will determine the transcriptional response to specific bacterial virulence factors or PAMPs in B. pseudomallei, including the type III and VI secretion systems, actin polymerization, flagellin and quorum sensing. We will computationally identify specific transcription factors that are activated and identify the compendium of genes that each of three transcription factor regulates. Finally, we will validate the transcriptional networks that are defined and determine their effect on B. pseudomallei infection in vivo and in vitro.

Public Health Relevance

This project focuses on the biodefense pathogen B. pseudomallei and the response to the organism by the innate immune system. The findings will have relevance to the early response to infection with this pathogen and may lead to treatment options that could be used in the event of a biological attack.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI057141-10
Application #
8447086
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
10
Fiscal Year
2013
Total Cost
$920,220
Indirect Cost
$289,920
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Majerczyk, Charlotte; Schneider, Emily; Greenberg, E Peter (2016) Quorum sensing control of Type VI secretion factors restricts the proliferation of quorum-sensing mutants. Elife 5:
Miller, Samuel I; Chaudhary, Anu (2016) A Cellular GWAS Approach to Define Human Variation in Cellular Pathways Important to Inflammation. Pathogens 5:
Jorgensen, Ine; Zhang, Yue; Krantz, Bryan A et al. (2016) Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis. J Exp Med 213:2113-28
Jorgensen, Ine; Lopez, Joseph P; Laufer, Stefan A et al. (2016) IL-1β, IL-18, and eicosanoids promote neutrophil recruitment to pore-induced intracellular traps following pyroptosis. Eur J Immunol 46:2761-2766
Chapman, John D; Edgar, J Scott; Goodlett, David R et al. (2016) Use of captive spray ionization to increase throughput of the data-independent acquisition technique PAcIFIC. Rapid Commun Mass Spectrom 30:1101-7
Hayden, Hillary S; Matamouros, Susana; Hager, Kyle R et al. (2016) Genomic Analysis of Salmonella enterica Serovar Typhimurium Characterizes Strain Diversity for Recent U.S. Salmonellosis Cases and Identifies Mutations Linked to Loss of Fitness under Nitrosative and Oxidative Stress. MBio 7:e00154
Fan, Vincent S; Gharib, Sina A; Martin, Thomas R et al. (2016) COPD disease severity and innate immune response to pathogen-associated molecular patterns. Int J Chron Obstruct Pulmon Dis 11:467-77
Yen, Gloria S; Edgar, J Scott; Yoon, Sung Hwan et al. (2016) Polydimethylsiloxane microchannel coupled to surface acoustic wave nebulization mass spectrometry. Rapid Commun Mass Spectrom 30:1096-100
Salipante, Stephen J; Roach, David J; Kitzman, Jacob O et al. (2015) Large-scale genomic sequencing of extraintestinal pathogenic Escherichia coli strains. Genome Res 25:119-28
Maltez, Vivien I; Tubbs, Alan L; Cook, Kevin D et al. (2015) Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium. Immunity 43:987-97

Showing the most recent 10 out of 240 publications