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Modeling leukocyte-leukocyte non-contact interactions in a lymph node
Nicola Gritti1, Michele Caccia, Laura Sironi
1Dipartimento di Fisica, Università degli studi di Milano-Bicocca, Milano, Italy.
Insights
Non-contact interactions, mediated by chemokines, significantly influence leukocyte behavior and interaction duration. Our model shows these non-contact forces play a crucial role in immune cell communication.
Area of Science:
- Immunology
- Biophysics
- Computational Biology
Background:
- Leukocyte interactions are fundamental to immune responses, involving both direct cell-cell contact and non-contact communication via chemokines.
- Understanding the impact of non-contact interactions on leukocyte kinematics and interaction duration is crucial for deciphering immune dynamics.
Purpose of the Study:
- To quantify the effect of non-contact interactions on leukocyte kinematics and interaction duration.
- To develop a simplified mean-field model for leukocyte-leukocyte interactions based on chemotaxis.
Main Methods:
- Adopted a simplified mean-field description inspired by the Keller-Segel chemotaxis model.
- Derived an analytical solution for slowly varying chemokine sources.
- Simulated leukocyte-leukocyte interactions using a space-dependent friction coefficient and the derived analytical solution.
- Compared simulation results with experimental data for dendritic cell (DC)-natural killer (NK) cell interactions.
Main Results:
- Developed a time-space separable mean field interaction force dependent on chemotaxis sensitivity, chemokine diffusion, and degradation rates.
- The model accurately predicted the percentage of leukocyte-leukocyte interactions within the experimental range.
- A ~25% increase in interactions was observed with increased chemotactic parameter, highlighting the significance of non-contact forces.
Conclusions:
- Non-contact interactions, driven by chemokine gradients, exert a non-negligible direct effect on leukocyte interactions and their duration.
- The developed Keller-Segel-inspired model provides a valuable framework for studying immune cell communication dynamics.
- Findings suggest that modulating chemokine signaling could be a therapeutic strategy for immune response regulation.
Abstract:
The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines) allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field description inspired by the Keller-Segel chemotaxis model, of which we report an analytical solution suited for slowly varying sources of chemokines. Since our focus is on the non-contact interactions, leukocyte-leukocyte contact interactions are simulated only by means of a space dependent friction coefficient of the cells. The analytical solution of the Keller-Segel model is then taken as the basis of numerical simulations of interactions between leukocytes and their duration. The mean field interaction force that we derive has a time-space separable form and depends on the chemotaxis sensitivity parameter as well as on the chemokines diffusion coefficient and their degradation rate. All these parameters affect the distribution of the interaction durations. We draw a successful qualitative comparison between simulated data and sets of experimental data for DC-NK cells interaction duration and other kinematic parameters. Remarkably, the predicted percentage of the leukocyte-leukocyte interactions falls in the experimental range and depends (~25% increase) upon the chemotactic parameter indicating a non-negligible direct effect of the non-contact interaction on the leukocyte interactions.
