#FEMSmicroBlog: Lipid droplets & antiviral immunity

02-02-2021

Lipid droplets are small membrane-bound organelles that are found in most cell types in the human body. They have long been thought of as small insignificant organelles with the sole purpose of providing an energy source to fuel cellular functions, but over the last ten years a lot of research has shed light on how multifaceted these organelles actually are. Karla Helbig and Ebony Monson, co-authors of the review “Lipid droplets and lipid mediators in viral infection and immunity” in FEMS Microbiology Reviews, tell more in the #FEMSmicroBlog. #FascinatingMicrobes 

 

Lipid droplets: Composition, role, functions

Lipid droplets are made up of a diverse array of lipid classes, with the membrane composed of phospholipids and the core containing mainly triglycerides and sterol esters. Work by many laboratories globally has demonstrated that lipid droplets are induced upon infection of cells by pathogens and, most recently, highlighted this response following viral infections.

For many years it was thought that viruses may induce lipid droplets as a fuel source for their own replication cycles. However, we are now gaining a greater understanding of the roles that these organelles play in effective host strategies against viral pathogens.

The host antiviral response is enhanced by lipid droplet upregulation. Lipid droplets are known sites of immune protein localisation and they are able to enhance immune signalling pathways. They are also the sites of important bioactive lipid mediator synthesis.

Lipid droplets are known sites of immune protein localisation and they are able to enhance immune signalling pathways.

Lipid droplets have recently been described as signalling hubs for important immune proteins during infection.  Host effector proteins such as viperin, CAMP, IRG family members, and helicases such as DDX3 and DDX1 localise to lipid droplets and play a role in the production of a successful immune response to pathogens.

In some cases, we know that the localisation of these immune proteins to lipid droplets is essential to produce effective antiviral responses (as the case for viperin). However, the way many of these proteins are targeted to lipid droplets and the mechanism of action behind this localisation is still unknown albeit a growing area of interest.

The way many immune proteins are targeted to lipid droplets and the mechanism of action behind this localisation is still unknown.

 

Lipid droplets: A paradigm shift

Viral infection upregulates lipid droplets, enhancing a number of innate immune signalling pathways. Upregulation of lipid droplets is able to enhance production of type-I interferon (one of the most potent antiviral cytokines), and is also critical for dendritic cell antigen cross-presentation.

Bioactive lipid mediators are important signalling molecules that can be synthesised on demand from cellular membranes as well as from lipid derived from lipid droplets.  Bioactive eicosanoid lipid mediators such as prostaglandins, leukotrienes and lipoxins are amongst the most studied of these signalling molecules in regard to their interaction with viral life cycles.

Their roles are known to be both pro-host or pro-viral depending on the cell type and the viral infection, but interestingly, there hasn’t been yet a great focus on the mechanisms behind how these lipid mediators actually work, leaving a potentially large gap in the field.

Pro-host and pro-virus effects of lipid mediators in viral infection (for more details, see the review).
Lipid mediators can be pro-host or pro-virus, yet there hasn’t been yet a great focus on the mechanisms behind how they actually work, leaving a potentially large gap in the field.

The roles of lipid droplets and the lipid species they harbour in antiviral immunity is in its infancy but gaining rapid momentum. There is a lot to learn from parallel fields which have studied the role of these critical organelles and their lipid species in more depth, finding them to play pivotal roles in multiple cell signalling and immune pathways, metabolic reprogramming, and activation of immune cells.

Our review explores the role of lipid droplets and important bioactive lipid mediators synthesised from lipid droplets in viral infections. We propose a paradigm shift in thinking in the field – whereby lipid droplets play pivotal roles in protecting the host against viral infection.

 

About the authors of this blog

Karla J Helbig is an associate Professor of Virology, and Head of the Discipline of Microbiology at La Trobe University, Melbourne (Australia). She obtained her PhD from Adelaide University, before undertaking postdoctoral training as an NHMRC fellow at the Royal Adelaide Hospital. Her research focuses on the use of advanced imaging, and molecular and genomic techniques to examine the cellular and molecular mechanisms of the host response to viral infection. Together with Ebony Monson, and her team she has been investigating links between the role of lipid droplets and an effective immune response against pathogenic organisms.

About this blog section

The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.

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