A single bacterium is not sufficient to trigger directional migration in neutrophils, allowing fast neutrophil recruitment to focal damage points

Session

Poster Session

Authors

Eva Mulder (2), Leonardo Zanella (2), Wiebe Buitenwerf (2), Elena Pascual Garcia (1), Joost Beltman (1), Nienke Vrisekoop (2)

Affiliations

1. Leiden University
2. UMC Utrecht

Abstract text

Introduction
 NEUTROPHILS are the elite cell type to fight bacterial infections. Nevertheless, intravital microscopy in mice show their scarce ability to recognize scattered single bacteria in the tissue. These observations are unexpected and subvert the classical view of neutrophils.

We use an in-vitro model of wound-like tissue to study human neutrophil 3D migration in order to clarify whether neutrophils are able to recognize a single bacterium.

Methods
 Live imaging of stained human neutrophils was carried out in 3D fibrinogen matrixes infected with different concentrations and configurations of S.aureus. Neutrophil migration was analyzed with IMARIS and R to determine directionality, displacement and speed.

Results
 Neutrophils are significantly directed towards big agglomerates of bacteria, while they fail to recognize single CFU. Similarly, cell displacement occurs only towards big bacteria clusters.

Neutrophils concomitantly show consistent reduction of speed after phagocytosis of bacteria, and confinement around the phagocytic region. Such confinement could be reversed by applying a strong chemotactic gradient, suggesting a regulation of the process rather than a simple physical constraint of the cell after phagocytosis.

Conclusion
 Neutrophils evolved to ignore single scattered bacteria while they migrate in an infected tissue. The ability to avoid smaller threats may allow redirection and faster arrival towards focal damage points, where immediate response is required. Lack of this ability could hinder efficient containment of large infected areas, restricting initial response to the periphery and leading to poorer outcomes.