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dc.contributor.authorBoribon, Brittany P.en
dc.contributor.authorLenzi, Mark J.en
dc.contributor.authorLi, Liwuen
dc.contributor.authorJones, Caroline N.en
dc.identifier.citationBoribong BP, Lenzi MJ, Li L and Jones CN (2019) Super-Low Dose Lipopolysaccharide Dysregulates Neutrophil Migratory Decision-Making. Front. Immunol. 10:359. doi: 10.3389/fimmu.2019.00359en
dc.description.abstractNeutrophils are the first responders to infection and play a pivotal role in many inflammatory diseases, including sepsis. Recent studies have shown that lipopolysaccharide (LPS), a classical pattern recognition molecule, dynamically programs innate immune responses. In this study, we show that pre-treatment with super-low levels of LPS [1 ng/mL] significantly dysregulate neutrophil migratory phenotypes, including spontaneous migration and altering neutrophil decision-making. To quantify neutrophil migratory decision-making with single-cell resolution, we developed a novel microfluidic competitive chemotaxis-chip (μC³) that exposes cells in a central channel to competing chemoattractant gradients. In this reductionist approach, we use two chemoattractants: a pro-resolution (N-Formyl-Met-Leu-Phe, fMLP) and pro-inflammatory (Leukotriene B₄, LTB₄) chemoattractant to model how a neutrophil makes a decision to move toward an end target chemoattractant (e.g., bacterial infection) vs. an intermediary chemoattractant (e.g., inflammatory signal). We demonstrate that naïve neutrophils migrate toward the primary end target signal in higher percentages than toward the secondary intermediary signal. As expected, we found that training with high dose LPS [100 ng/mL] influences a higher percentage of neutrophils to migrate toward the end target signal, while reducing the percentage of neutrophils that migrate toward the intermediary signal. Surprisingly, super-low dose LPS [1 ng/mL] significantly changes the ratios of migrating cells and an increased percentage of cells migrate toward the intermediary signal. Significantly, there was also an increase in the numbers of spontaneously migrating neutrophils after treatment with super-low dose LPS. These results shed light onto the directional migratory decision-making of neutrophils exposed to inflammatory training signals. Understanding these mechanisms may lead to the development of pro-resolution therapies that correct the neutrophil compass and reduce off-target organ damage.en
dc.description.sponsorshipResearch materials and equipment for this study were funded by the Department of Biological Sciences at Virginia Tech. BB was supported by the VT-Initiative for Maximizing Student Development (IMSD) (NIGMS 2R25GM072767-05A1). LL is supported by NIH R01 AI136386.en
dc.format.extent12 pagesen
dc.rightsAttribution 4.0 Internationalen
dc.subjectneutrophil memoryen
dc.titleSuper-Low Dose Lipopolysaccharide Dysregulates Neutrophil Migratory Decision-Makingen
dc.typeArticle - Refereeden
dc.title.serialFrontiers in Immunologyen

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Attribution 4.0 International
License: Attribution 4.0 International