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Immune surveillance of cellular homeostasis by NOD1/2 via sensing cytosolic sphingosine-1-phosphate (S1P)

ABSTRACT: Chronic inflammation is associated with disruption of cellular homeostasis, yet the underlying mechanisms remain elusive1. Nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2) are intracellular pathogen recognition receptors that activate innate immune responses via sensing bacterial peptidoglycans2-4. We demonstrate that NOD1/2 sense not only microbe-specific molecular patterns but also perturbation of cell homeostasis, and thereby cause inflammation. Host generation of sphingosine-1-phosphate (S1P) via the hydrolysis pathway is essential for NOD1/2 signaling upon such stress. Cytosolic delivery of S1P activates NOD1/2 dependent NF-κB activation and inflammation. Finally, we demonstrate that S1P directly binds to and activates NOD1/2. In sum, we describe a hitherto unknown role of NOD1/2 by revealing that they initiate innate immune responses by surveillance of cellular homeostasis through sensing of cytosolic S1P. Our findings provide a novel link between host cytosolic S1P and NOD1/2 mediated immune activation upon perturbation of cellular homeostasis and thus form the basis for future intervention strategies targeting the S1P-NOD1/2 axis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE124828 | GEO | 2020/01/01

REPOSITORIES: GEO

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Immune surveillance of cellular homeostasis by NOD1/2 via sensing cytosolic sphingosine-1-phosphate (S1P)

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