A novel role for lipid droplets in the organismal antibacterial response

Abstract

We previously discovered histones bound to cytosolic lipid droplets (LDs); here we show that this forms a cellular antibacterial defense system. Sequestered on droplets under normal conditions, in the presence of bacterial lipopolysaccharide (LPS) or lipoteichoic acid (LTA), histones are released from the droplets and kill bacteria efficiently in vitro. Droplet-bound histones also function in vivo: when injected into Drosophila embryos lacking droplet-bound histones, bacteria grow rapidly. In contrast, bacteria injected into embryos with droplet-bound histones die. Embryos with droplet-bound histones displayed more than a fourfold survival advantage when challenged with four different bacterial species. Our data suggests that this intracellular antibacterial defense system may function in adult flies, and also potentially in mice.

DOI: http://dx.doi.org/10.7554/eLife.00003.001

eLife digest

Histones are proteins found in large numbers in most animal cells, where their primary job is to help DNA strands fold into compact and robust structures inside the nucleus. In vitro, histones are very effective at killing bacteria, and there is some evidence that histones secreted from cells provide protection against bacteria living outside cells. However, many types of bacteria are able to enter cells, where they can avoid the immune system and go on to replicate.

In principle histones could protect cells against such bacteria from the inside, but for many years this was thought to be unlikely because most histones are bound to DNA strands in the cell nucleus, whereas the bacteria replicate in the cytosol. Moreover, free histones can be extremely damaging to cells, so most species have developed mechanisms to detect and degrade free histones in the cytosol.

Recently, however, it was discovered that histones can bind to lipid droplets—organelles in the cytosol that are primarily used to store energy—in various animal cells and tissues. Now, Anand et al. have demonstrated that histones bound to lipid droplets can protect cells against bacteria without causing any of the harm normally associated with the presence of free histones. In in vitro experiments with lipid droplets purified from Drosophila embryos, they showed that histones bound to lipid droplets could be released to kill bacteria. The histones were released by lipopolysaccharide or lipoteichoic acid produced by the bacteria.

The effect was also observed in vivo: using four different bacterial species, Anand et al. injected similar numbers of bacteria into Drosophila embryos that contained histones bound to lipid droplets, and also into embryos that had been genetically modified so that they did not contain such droplet-bound histones. While most of the normal embryos survived, the vast majority of the embryos without droplet-bound histones died. Similar results were also found in experiments on adult flies, along with evidence which suggests that histones might also provide defenses against bacteria in mice.

DOI: http://dx.doi.org/10.7554/eLife.00003.002