Researchers find a cellular defence mechanism against viral and bacterial infections

IDIBAPS and UB research group: Marta Bosch, Albert Pol, Alba Fajardo and Frederic Morales Paytuví. Image: Francisco Avia

IDIBAPS and UB research group: Marta Bosch, Albert Pol, Alba Fajardo and Frederic Morales Paytuví. Image: Francisco Avia

A study published in the journal Science and coordinated by researchers from IDIBAPS and the University of Barcelona describes a mechanism of immunologic defence which was unknown until now. It is a strategy built by lipid bodies (LB), cellular organelles able to attract and remove invasive pathogens.

The research was carried out as a part of an international project funded by the Human Frontier Science Program. Among the participants are researchers from Spain, United States, Australia and Brazil, with the collaboration from scientists from CNIC and IIBB-CSIC. The study was coordinated by Albert Pol, adjunct lecturer at the Faculty of Medicine and Health Sciences of the UB and ICREA professor at IDIBAPS, where he leads the team Lipid Trafficking and Disease, and Robert G. Parton, from the Institute of Molecular Biosciences of the University of Queensland. The first authors of the article are Marta Bosch, researcher at the mentioned team from IDIBAPS, and Miguel Sánchez Álvarez, from the group on Mechanoadaption and Caveolas Biology at CNIC.

Lipid bodies are organelles where our cells accumulate nutrients that, in form of fat, provide the necessary energy so these can develop their function. For instance LBs provide the heart with the energy to beat, and the liver can also carry out its metabolic function, and muscles can move. “The lipid droplet is like a pantry for cells, where we accumulate the food we will use later. This happens in eukaryotic cells, from yeasts or insects to plants or mammals”, notes Albert Pol.

When virus and bacteria infect the host cell, they need a great number of nutrients to multiply and get them to reach the LB. In the study published in Science, researchers showed that, as a response to the infection, LBs organize complexes of antibiotic and antiviral proteins that act cooperatively to fight the pathogen and remove it. This mechanism would work in all body cells, not only in those of the immune system such as macrophages. The fact that this has been observed in insects too suggests the importance of this defence strategy during the evolution of our innate immunity.

The key to the innate immunity of cells

Researchers showed that in order to protect themselves from the infection, the cells place a great amount of antibiotic and antiviral proteins in the LBs. compared to the surface of LBs in normal and infected cells, the study identified four hundred candidates that would conduct the function to protect LBs when these are in contact with the pathogen. “In this study, we focused on six of those cells and we showed that they really protect from three types of bacteria during the infection”, notes Marta Bosch.

“The concentration of these antibiotic and antiviral proteins in a single compartment inside the cell allows creating synergies while reducing their toxicity and allowing the rest of the cellular machinery to function normally,” says Miguel Sánchez-Álvarez.

Also, the study shows this strategy allows a wide-spectrum response, that is, there are many antibiotic and antivirals with different action mechanisms. It also enables creating cooperative mechanisms to attack the infection: “There are synergies between proteins, and, for example, one breaks the membrane of the pathogen and the other destroys its genomic material,” authors say.

“This study represents a paradigm shift since until now it was thought that LDs were at the service of viruses or bacteria during infection,” says Albert Pol. “Given the widespread resistance to current antibiotics, this study has deciphered an important defence mechanism that could be used for the development of new therapeutic strategies to stop infections,” he concludes.

Article reference:

M. Bosch et al. “

Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense

“. Science, Science 16 Oct 2020: Vol. 370, Issue 6514, eaay8085. DOI: 10.1126/science.aay8085

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