Blurred line between chemotactic chase and phagocytic consumption: an immunophysical single-cell perspective

Abstract

Chemotaxis and phagocytosis by innate immune cellsAt a first glance, the distinction between phagocytosis and chemotaxis appears straightforward. On the one hand, classical Summary An innate immune cell can sense a pathogen, either from a distance by recognizing chemoattractant stimuli or by direct physical contact. The pathogen is subsequently neutralized, which usually occurs through its phagocytic internalization. By investigating chemotaxis and phagocytosis from an immunophysical single-cell perspective, it now appears that the demarcation between these two processes is less distinct than originally thought. Several lines of evidence support this notion. First, chemotactic stimulation does not cease at the moment of initial contact between the cell and the pathogenic target. Second, even when classical chemotaxis of neutrophils is suppressed, the early cell response to contact with typical chemoattractant targets, such as zymosan, fungal spores or chemokine-coated particles, can still involve morphological attributes of chemotaxis. Recognizing that the changing morphology of motile cells is inextricably linked to physical cell behavior, this Commentary focuses on the mechanical aspects of the early response of innate immune cells to chemotactic and phagocytic stimuli. On the basis of this perspective, we propose that the combined study of chemotaxis and phagocytosis will, potentially, not only advance our grasp of the mechanisms underlying immune-cell motility but also open new lines of research that will promote a deeper understanding of the innate recognition of pathogens.

Controlled One-on-One Encounters between Immune Cells and Microbes Reveal Mechanisms of Phagocytosis

“…A local stimulus acting at the cell surface leads to reorganization of the adjacent cytoskeleton, which in turn creates a pushing force that displaces a membrane patch outward. This basic mechanism is consistent with the cell morphology observed during pure (i.e., cell-substrate-adhesion-free) chemotaxis (9)(10)(11)33). But it also implies that immediately after cell-target contact, a phagocyte should always form a protrusive pseudopod directly underneath the region of contact (where the phagocytosis-triggering stimulus is strongest).…”

“…1 B), and have already revealed insight into cellular behavior that had been inaccessible to traditional techniques. (For movies of representative single-live-cell experiments see https://www.youtube.com/user/HeinrichLab or the supplemental videos of (7,(9)(10)(11)(12)). …”

Canonical and Noncanonical G-Protein Signaling Helps Coordinate Actin Dynamics To Promote Macrophage Phagocytosis of Zymosan

“…Initial macrophage-pathogen encounters are driven by canonical G-protein signaling (3). Cell polarization, chemotaxis, directed cell protrusions, and cell ruffling all depend upon the release of G␤␥ subunits from G␣ i (5,36).…”

“…Although largely studied independently, phagocytosis and chemotaxis share morphological attributes (3). Both processes converge on signaling to the cytoskeleton, require cell membrane remodeling, and depend upon actin-driven cell protrusions.…”

Quantifying the Sensitivity of Human Immune Cells to Chemoattractant

“…Recent single-cell experiments have validated human neutrophils as uniquely capable biodetectors of minuscule amounts of complement-derived anaphylatoxins in the proximity of microbial and model pathogens ( Fig. 1) (6)(7)(8). But the question just how sensitive these immune cells are was not addressed by earlier studies.…”