About this Research Topic
Sphingolipids are major components of membranes and as such, their spatiotemporal accumulation levels substantially determine membrane biophysical properties. Both under homeostatic conditions or regulation by external cues, sphingolipid turnover and composition impact on membrane integrity and dynamics, and on sorting of membrane integral or associated proteins, best exemplified by segregation of surface receptors and trafficking and recruitment of associated signalosomes. Thereby, breakdown of complex sphingolipids and release of bioactive sphingolipid metabolites such as ceramides, sphingosine and sphingosine-1-phosphate effectively take part in many cellular responses including stress and apoptosis, but also cell survival, expansion and directional motility.
Targeted intervention in sphingolipid turnover has proven to be a successful strategy in cancer and inflammation and though of obvious importance there, its potential as target in controlling infectious diseases is just being explored since more recently. Meanwhile, sphingolipids are recognized as important regulators in 1) pathogen – host cell interactions such as entry, trafficking, subcellular compartmentalization, egress and spread, 2) cell autonomous and innate immune defense, and 3) activity, differentiation and compartmentalization of antigen presenting and immune effector cells. Moreover, some of their bioactive species act directly bacteriocidal. Altogether, this has coined them as promising targets/effectors for (immune)therapeutic interventions in infectious diseases.
Understanding of cell compartments, pathways and mediators targeted by sphingolipids in infection control was substantially fueled by progress made at the technical level. This includes 1) novel analytical approaches allowing highly sensitive detection of distinct sphingolipid species, 2) synthesis and adaptation of bio-orthogonally functionalized sphingolipids allowing for visualization of their trafficking, compartmentalization domain organization and protein interactions, 3) high resolution microscopy approaches, and 4) availability of novel mouse strains allowing for conditional compartment specific ablation of sphingolipid metabolizing enzymes. It is especially the last item, that holds particular promise in perpetuing studies on the role of sphingolipids in infection control and to evaluate potential therapeutic compounds and/or strategies.
This Research Topic aims at providing insight into the current state of the art in the role of sphingolipid metabolism and its compartmentalization in the control of infectious diseases with particular emphasis on cellular/organismic targets of intervention. We welcome researchers to submit abstracts of their Original Research, Research Opinions, and Reviews directly relating to the Research Focus subject. Centering on sphingolipid dynamics, we welcome contributions including the following topics :
1. Pathogen interaction with its target cells and tissue
2. Regulation of innate and adaptive immunity
3. Mechanisms of bacteriocidal/virostatic activity
4. Translational application
5. Technical advances in synthesis and analytics
The Guest Editors Sibylle Schneider-Schaulies, Jürgen Seibel and Burkhard Kleuser, declare that they are affiliated with the DFG Research Unit 2123 on Sphingolipid dynamics in infection control.
Keywords: bio-orthogonal chemistry and high end analytics, (immuno)therapeutic potential, Sphingolipid metabolism, pathogen host cell interaction, innate and adaptive immunity