Journal article
Detecting lipopolysaccharide in the cytosol of mammalian cells: Lessons from MD-2/TLR4
Journal of leukocyte biology, Vol.106(1), pp.127-132
07/2019
DOI: 10.1002/JLB.3MIR1118-434R
PMCID: PMC6597272
PMID: 30694581
Abstract
Proinflammatory immune responses to Gram-negative bacterial lipopolysaccharides (LPS) are crucial to innate host defenses but can also contribute to pathology. How host cells sensitively detect structural features of LPS was a mystery for years, especially given that a portion of the molecule essential for its potent proinflammatory properties-lipid A-is buried in the bacterial membrane. Studies of responses to extracellular and vacuolar LPS revealed a crucial role for accessory proteins that specifically bind LPS-rich membranes and extract LPS monomers to generate a complex of LPS, MD-2, and TLR4. These insights provided means to understand better both the remarkable host sensitivity to LPS and the means whereby specific LPS structural features are discerned. More recently, the noncanonical inflammasome, consisting of caspases-4/5 in humans and caspase-11 in mice, has been demonstrated to mediate responses to LPS that has reached the host cytosol. Precisely how LPS gains access to cytosolic caspases-and in what form-is not well characterized, and understanding this process will provide crucial insights into how the noncanonical inflammasome is regulated during infection. Herein, we briefly review what is known about LPS detection by cytosolic caspases-4/5/11, focusing on lessons derived from studies of the better-characterized TLR4 system that might direct future mechanistic questions.
Details
- Title: Subtitle
- Detecting lipopolysaccharide in the cytosol of mammalian cells: Lessons from MD-2/TLR4
- Creators
- Jason H Barker - The Veterans Affairs Medical Center, Iowa City, Iowa, USAJerrold P Weiss - The Veterans Affairs Medical Center, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Journal of leukocyte biology, Vol.106(1), pp.127-132
- DOI
- 10.1002/JLB.3MIR1118-434R
- PMID
- 30694581
- PMCID
- PMC6597272
- ISSN
- 0741-5400
- eISSN
- 1938-3673
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01 AI104728 / NIAID NIH HHS
- Language
- English
- Date published
- 07/2019
- Academic Unit
- Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094567002771
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