Macrophages monitor tissue osmolarity and induce inflammatory response through NLRP3 and NLRC4 inflammasome activation

Wai Kee Eddie Ip, Ruslan Medzhitov

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Interstitial osmolality is a key homeostatic variable that varies depending on the tissue microenvironment. Mammalian cells have effective mechanisms to cope with osmotic stress by engaging various adaptation responses. Hyperosmolality due to high dietary salt intake has been linked to pathological inflammatory conditions. Little is known about the mechanisms of sensing the hyperosmotic stress by the innate immune system. Here we report that caspase-1 is activated in macrophages under hypertonic conditions. Mice with high dietary salt intake display enhanced induction of Th17 response upon immunization, and this effect is abolished in caspase-1-deficient mice. Our findings identify an unknown function of the inflammasome as a sensor of hyperosmotic stress, which is crucial for the induction of inflammatory Th17 response.

Original languageEnglish (US)
Article number6931
JournalNature communications
Volume6
DOIs
StatePublished - May 11 2015
Externally publishedYes

Fingerprint

Inflammasomes
Caspase 1
macrophages
Macrophages
Osmolar Concentration
monitors
Salts
Chemical activation
activation
Tissue
Immunization
mice
Immune system
Osmotic Pressure
induction
salts
immune systems
Immune System
Display devices
Cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Macrophages monitor tissue osmolarity and induce inflammatory response through NLRP3 and NLRC4 inflammasome activation. / Ip, Wai Kee Eddie; Medzhitov, Ruslan.

In: Nature communications, Vol. 6, 6931, 11.05.2015.

Research output: Contribution to journalArticle

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