Abstract

The innate immune system is essential for the immediate response to infectious challenge. It is nowapparent that Toll-like receptors (TLR) are key in mediating this response by the recognition of ligandsexpressed by a wide variety of infectious agents. It has been demonstrated in mouse models thatstimulation of the innate immune system by TLR ligands results in a transiently heightened nonspecific stateof resistance to some infections. Furthermore, activation of the innate immune system by the use ofadjuvants during vaccination is necessary for the development of an antigen-specific immune response.However, the identity of the antigen presenting cell (or cells) as well as the exact signals that are delivered tothose cells by adjuvants are unknown. Species-specific differences in the expression pattern of TLRs aswell as in the ligands recognized by specific TLRs have been demonstrated, suggesting that primate modelsmay be more predictive of human responses than mouse models in response to TLR ligands. We thereforepropose to carefully dissect the activation of various ARC populations by defined TLR ligands in vitro and toexamine effector responses generated to model antigens combined with specific TLR ligands in vivo.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
3U54AI057141-05S1
Application #
7639068
Study Section
Special Emphasis Panel (ZAI1-KLW-M (M3))
Project Start
2008-03-01
Project End
2009-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
5
Fiscal Year
2008
Total Cost
$288,061
Indirect Cost

  Institution

Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Hagar, Jon A; Edin, Matthew L; Lih, Fred B et al. (2017) Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock. J Immunol 199:3634-3643
Hajjar, Adeline M; Ernst, Robert K; Yi, Jaehun et al. (2017) Expression level of human TLR4 rather than sequence is the key determinant of LPS responsiveness. PLoS One 12:e0186308
Jorgensen, Ine; Lopez, Joseph P; Laufer, Stefan A et al. (2016) IL-1?, IL-18, and eicosanoids promote neutrophil recruitment to pore-induced intracellular traps following pyroptosis. Eur J Immunol 46:2761-2766
Miller, Samuel I; Chaudhary, Anu (2016) A Cellular GWAS Approach to Define Human Variation in Cellular Pathways Important to Inflammation. Pathogens 5:
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
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
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
Chaudhary, Anu; Leite, Mara; Kulasekara, Bridget R et al. (2016) Human Diversity in a Cell Surface Receptor that Inhibits Autophagy. Curr Biol 26:1791-801
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:
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

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