De Novo sphingolipid synthesis is essential for Salmonella-induced autophagy and human beta-defensin 2 expression in intestinal epithelial cells.

Fu-Chen Huang

doi:10.1186/s13099-016-0088-2

Abstract

BackgroundSphingolipids are important for innate immune response to eliminate infected pathogens and involved in autophagy. On the other hand, nucleotide-binding oligomerization domain-containing protein 2 (NOD2) served as an intracellular pattern recognition receptor to enhance host defense by inducing autophagy and the production of antimicrobial peptides, such as human beta-defensin-2 (hBD-2). However, the role of sphingolipids in Salmonella-induced autophagy and hBD-2 response in intestinal epithelial cells has not been previously elucidated.MethodsSalmonella typhimurium wild-type strain SL1344 was used to infect SW480, an intestinal epithelial cell. hBD-2 and interleukin-8 (IL-8) mRNA expressions were assessed in SW480 cells using RT-PCR, and intracellular signaling pathways and autophagy protein expression were analyzed by Western blot in SW480 cells in the presence or absence of inhibitors or transfected with siRNA.ResultsWe demonstrated that inhibition of de novo sphingolipid synthesis repressed the membrane recruitment of NOD2 and autophagy-related protein 16-like 1 (Atg16L1), suppressed Salmonella-induced autophagic protein LC3-II expression, and reduced NOD2-mediated hBD-2 response in Salmonella-infected SW480 cells. Contrasting to the utilization of membrane cholesterol on maintenance of Salmonella-containing vacuoles and anti-inflammation by Salmonella, sphingolipids act on epithelial defense against the invasive pathogen.ConclusionsOur results offer mechanistic insights on the role of de novo sphingolipid synthesis in the innate immunity of intestinal epithelial cells to Salmonella infection. The pharmaceuticals enhancing or diet enriched with sphingolipids may induce the dual anti-bacterial mechanisms. The role of de novo sphingolipid synthesis on inflammatory bowel disease is deserved to be further investigated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13099-016-0088-2) contains supplementary material, which is available to authorized users.

Highlights

Sphingolipids are important for innate immune response to eliminate infected pathogens and involved in autophagy
We examine if membrane sphingolipids play a crucial role on the Salmonella-induced autophagy and human beta-defensin-2 (hBD-2) response in intestinal epithelial cell (IEC) via nucleotide-binding oligomerization domain-containing protein 2 (NOD2)
Inhibition of de novo sphingolipid synthesis suppresses autophagy proteins expression of Salmonella‐infected SW480 cells Sphingolipids are a class of bioactive lipids that mediate many key cellular processes, including apoptosis and autophagy [15]

Summary

Introduction

Sphingolipids are important for innate immune response to eliminate infected pathogens and involved in autophagy. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) served as an intracellular pattern recognition receptor to enhance host defense by inducing autophagy and the production of antimicrobial peptides, such as human beta-defensin-2 (hBD-2). The role of sphingolipids in Salmonella-induced autophagy and hBD-2 response in intestinal epithelial cells has not been previously elucidated. Sphingolipids are important for innate immune response to eliminate infected pathogens and play a crucial role in infectious diseases [3]. Sphingolipids are involved in the regulation of autophagy [4] and might potentially be novel targets for therapeutic intervention in human diseases [5]. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) recruiting autophagy-related

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Conclusion