期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 26, 页码 14694-14702出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2003034117
关键词
nitric oxide synthase-2 (NOS2); live imaging; phagosome; nitric oxide; microglia
资金
- Brain Research Foundation Scientific Innovation Award
- University of Chicago Women's Board
- Mergel Funsky award
- National Institute of Diabetes and Digestive and Kidney Diseases Centre [P30DK42086]
- Searle Funds at The Chicago Community Trust [C-084]
- University of Chicago
- Office of Naval Research, Department of Defense [N00014-18-126]
- Cure Alzheimer's Fund
Innate immune cells destroy pathogens within a transient organelle called the phagosome. When pathogen-associated molecular patterns (PAMPs) displayed on the pathogen are recognized by Toll-like receptors (TLRs) on the host cell, it activates inducible nitric oxide synthase (NOS2) which instantly fills the phagosome with nitric oxide (NO) to clear the pathogen. Selected pathogens avoid activating NOS2 by concealing key PAMPs from their cognate TLRs. Thus, the ability to map NOS2 activity triggered by PAMPs can reveal critical mechanisms underlying pathogen susceptibility. Here, we describe DNA-based probes that ratiometrically report phagosomal and endosomal NO, and can be molecularly programmed to display precise stoichiometries of any desired PAMP. By mapping phagosomal NO produced in microglia of live zebrafish brains, we found that single-stranded RNA of bacterial origin acts as a PAMP and activates NOS2 by engaging TLR-7. This technology can be applied to study PAMP-TLR interactions in diverse organisms.
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