Investigating Morphological Changes of T-lymphocytes after Exposure with Bacterial Determinants for Early Detection of Septic Conditions

Abstract

Sepsis is a leading cause of morbidity and mortality, annually affecting millions of people worldwide. Immediate treatment initiation is crucial to improve the outcome but despite great progress, early identification of septic patients remains a challenge. Recently, white blood cell morphology was proposed as a new biomarker for sepsis diagnosis. In this proof-of-concept study, we aimed to investigate the effect of different bacteria and their determinants on T-lymphocytes by digital holographic microscopy (DHM). We hypothesize that species- and strain-specific morphological changes occur, which may offer a new approach for early sepsis diagnosis and identification of the causative agent. Jurkat cells as a model system were exposed to different S. aureus or E. coli strains either using sterile determinants or living bacteria. Time-lapse DHM was applied to analyze cellular morphological changes. There were not only living bacteria but also membrane vesicles and sterile culture supernatant-induced changes of cell area, circularity, and mean phase contrast. Interestingly, different cellular responses occurred depending on both the species and strain of the causative bacteria. Our findings suggest that investigation of T-lymphocyte morphology might provide a promising tool for the early identification of bacterial infections and possibly discrimination between different causative agents. Distinguishing gram-positive from gram-negative infection would already offer a great benefit for the proper administration of antibiotics.

Development and validation of a machine learning-based interpretable model for predicting sepsis by complete blood cell parameters

“…It opens up new avenues for research, allowing us to gain a deeper understanding of the mechanisms of lymphocyte function and dysfunction. Recently, related studies have demonstrated that T lymphocytes exhibit different morphological changes following exposure to various bacterial determinants, providing further support for our findings [ 28 , 29 ]. Additionally, platelets play a vital role in immune response, pathogen clearance, tissue repair, hemostasis, and thrombosis.…”

Three-dimensional label-free morphology of CD8 + T cells as a sepsis biomarker

“…One promising avenue is the study of immune cell morphology. These morphological changes in immune cells occur swiftly upon the onset of inflammation, closely mirror the patient's immune status, and provide an immediate snapshot of the cellular responses to inflammation [24][25][26][27] . Advancements in microscopic techniques have enabled rapid and repeated measurements.…”

Computational nucleus specificity for holographic tomography in flow cytometry

“…Therefore, the phase-contrast is intrinsically related to the refractive index (RI) of the cell and to its morphology. The measurement of these parameters has been exploited in life sciences in several ways [4][5][6][7][8] . Thus, the latest evolution of QPI, namely tomographic phase microscopy (TPM), has further expanded and enhanced the range of labelfree biomedical applications 9,10 .…”