Microphysiological Systems for Studying Cellular Crosstalk During the Neutrophil Response to Infection

Abstract

Neutrophils are the primary responders to infection, rapidly migrating to sites of inflammation and clearing pathogens through a variety of antimicrobial functions. This response is controlled by a complex network of signals produced by vascular cells, tissue resident cells, other immune cells, and the pathogen itself. Despite significant efforts to understand how these signals are integrated into the neutrophil response, we still do not have a complete picture of the mechanisms regulating this process. This is in part due to the inherent disadvantages of the most-used experimental systems: in vitro systems lack the complexity of the tissue microenvironment and animal models do not accurately capture the human immune response. Advanced microfluidic devices incorporating relevant tissue architectures, cell-cell interactions, and live pathogen sources have been developed to overcome these challenges. In this review, we will discuss the in vitro models currently being used to study the neutrophil response to infection, specifically in the context of cell-cell interactions, and provide an overview of their findings. We will also provide recommendations for the future direction of the field and what important aspects of the infectious microenvironment are missing from the current models.

Systematic review of preclinical studies on the neutrophil-mediated immune response to air pollutants, 1980–2020

“…Preclinical study models, also called basic medical research, include experiments on animals, cellular studies, among others that seek to clarify biochemical, genetic, physiological, or immunological mechanisms for various purposes such as improving analytical, diagnostic, or therapeutic processes, as well as consolidating (and in some cases discarding) scientific knowledge that is indispensable for the subsequent development of research on patients. Animal models make it possible to visualize the neutrophil-mediated immune response in a physiologically relevant environment that includes cellular interactions or specific signals that can be evaluated by in vitro models [127,128]. In this review, it was evidenced that most of the studies included an in vivo model, in which mainly mice and rats were used.…”

Tissue Models for Neisseria gonorrhoeae Research—From 2D to 3D

“…The major advantage of microfluidics devices lies in their ability to allow single-cell analysis amidst neutrophil heterogeneity. Continuous development of such devices will allow extensive insights into signals controlling neutrophil function (Richardson et al, 2021).…”

“…With the addition of neutrophils to the top well, one can quantify the neutrophil migration to the bottom well. These models allow only end point analysis, and to monitor the real-time neutrophil migration and response more complex models are needed (Richardson et al, 2021).…”

An Individual Patient's “Body” on Chips—How Organismoid Theory Can Translate Into Your Personal Precision Therapy Approach

“…The academic MPS development landscape has provided a number of other indicators that particular elements of blood perfusion can be recapitulated using MPS. The capability of emulating platelet-induced blood coagulation has been demonstrated by Westein et al (140) and numerous publications describe the circulation of immune cells in MPS and their settlement in organ models on chips (141)(142)(143).…”