ETosis is a form of cell death, where immune cells release extracellular traps (ETs). ETs are formed in response to various stimuli, to trap/kill invading pathogens. The bi-component leukotoxin Panton-Valentine leukocidin (PVL), secreted by Staphylococcus aureus, has yet to be confirmed as an effector of ETosis. ETosis can be beneficial for pathogenic infections, but may also present negative effects such as tissue damage. Thus, it is essential to understand the signaling mechanisms of ETosis and identify specific signaling pathways in response to PVL.
We used primary human myeloblasts for ET observation, triggered by PVL. Cell culture assays, immunofluorescence and microscopy analyses were performed in various conditions, with variance analyses followed by Bonferroni’s corrections for significance testing. Transcriptomics were then applied to identify differential gene expression levels of PVL exposed vs. non-exposed cells with cufflinks/cuffdiff.
ET formation is observed in vitro in response to a broad spectrum of PVL concentrations. Differential expression analyses, showed a significant alteration in specific genes (p-values < 0.001), with either upregulations during PVL exposure or downregulations. Most of these genes are identified as key elements of several signaling pathways, known to be essential for ET formation.
We provide evidence that PVL may induce ET formation, which seems to alter the expression of specific genes of well-known signaling pathways, enabling the identification of adapted ETosis inhibitors. Findings, may lead towards the development of a therapy favoring bacterial clearance in severe infections, as this virulence factor is known to be involved in cell death resulting in extensive tissue damage.
Dr. Margaux Dreyer Is Currently A Postdoctoral Fellow At The Institute Of Microbiology Of The University Of Strasbourg, France. She Obtained An Early Postdoc Mobility Grant For 2017-2018 Awarded By The Swiss National Science Foundation. Margaux Completed Her PhD At The University Of Bern, Switzerland And Her Undergraduate Studies At The University Of Lausanne, Switzerland. Her Research Interests Lie In The Area Of Gram + Bacterial Infections And Their Effect On The Immune System Of Various Species.