ORCID Profile
0000-0003-1061-9790
Current Organisation
Northwestern University
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Publisher: Elsevier
Date: 2018
Publisher: S. Karger AG
Date: 18-03-2021
DOI: 10.1159/000513118
Abstract: Human neutrophils are highly sensitive to the presence of i Borrelia burgdorferi /i (Bb), the agent of Lyme disease (LD), in tissues. Although Bb is also found in the blood of LD patients, far less is known about how neutrophils respond to Bb in the presence of blood. In this study, we employed microfluidic tools to probe the interaction between human neutrophils and Bb and measured the activation of human neutrophils in blood s les from patients. We found that neutrophils migrate vigorously toward Bb in the presence of serum, and this process was complement-dependent. Preventing complement factor 5 cleavage or blocking complement receptors decreased neutrophil’s ability to interact with Bb. We also found that spiking Bb directly into the blood from healthy donors induced spontaneous neutrophil motility. This response to Bb was also complement-dependent. Preventing complement factor 5 cleavage decreased spontaneous neutrophil motility in Bb-spiked blood. Moreover, we found that neutrophils in blood s les from acute LD patients displayed spontaneous motility patterns similar to those observed in Bb-spiked s les. Neutrophil motility was more robust in blood s les from LD patients than that measured in healthy and ill controls, validating the utility of the microfluidic assay for the study of neutrophil-Bb interactions in the presence of blood.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8LC01263F
Abstract: Nanoliter-scale microfluidic arenas for imaging war games between human neutrophils and microbes at cellular resolution.
Publisher: Springer Science and Business Media LLC
Date: 19-03-2018
DOI: 10.1038/S41551-018-0208-Z
Abstract: Current methods for the diagnosis of sepsis have insufficient precision, causing regular misdiagnoses. Microbiological tests can help diagnose sepsis but are usually too slow to have an impact on timely clinical-decision making. Neutrophils have high sensitivity to infections, yet measurements of neutrophil surface markers, genomic changes, and phenotype alterations have had only a marginal effect on sepsis diagnosis. Here, we report a microfluidic assay that measures the spontaneous motility of neutrophils in the context of plasma, in one droplet of blood. We measured the performance of the assay in two independent cohorts of critically ill patients suspected of sepsis. In the first cohort, we developed a machine-learning-based scoring system (sepsis score) that segregated patients with sepsis from those without sepsis. In the second cohort, we validated the sepsis score in a double-blinded, prospective case-control study. For the 42 patients across the two cohorts, the assay identified sepsis patients with 97% sensitivity and 98% specificity. The neutrophil assay could potentially be used to accurately diagnose and monitor sepsis in larger populations of at-risk patients.
No related grants have been discovered for Anika Marand.