Cell Migration Guided by Cell-Cell Contacts in Innate Immunity

Abstract

The directed migration of leukocytes to sites of damage or infection is necessary for a productive immune response. There is substantial evidence supporting a key role for chemoattractants in directed migration, however, less is known about how cell-cell contacts affect the migratory behavior of leukocytes in innate immunity. Here, we explore how cell-cell contacts can affect the directed migration of innate immune cells, including their role in attracting, repelling, or stopping cell motility. Further investigation of cell contact dynamics as guidance cues may yield new insights into the regulation of innate immunity.

Keywords: cell–cell contact; macrophages; migration; neutrophils.

Figure 1.. Neutrophil swarming at inflammatory sites.

Neutrophils are recruited, aided by relay signals such as LTB4, and aggregate at the sites of damage or infection [19].

Figure 2.. Neutrophil-macrophage interaction during wound response.

In a zebrafish model of inflammation, macrophages physically interact with neutrophils at the wound site and exhibit neutrophil-repelling behavior. This interaction promotes neutrophil reverse migration away from the wound and thereby the resolution of inflammation [41].

Figure 3.. Macrophage-tumor cell interaction during tumor cell intravasation.

In vitro and mouse model of breast cancer revealed that physical contact between macrophages and tumor cells induces invadopodia formation in tumor cells that in turn enables tumor cells to breach the basement membrane and intravasate [72].

Figure 4.. Stop signal delivered by antigen presenting cells.

Antigen presenting cells (APC), such as dendritic cells, provide a stop signal that halt randomly migrating T cells to allow stable interaction for efficient T cell activation at the immunological synapse (IS) [75].

Text Box Figure I.

Migratory contact responses by slow-moving cells. A) A type of contact inhibition of locomotion behavior where head-to-head collision may result in interacting cells repelling each other [2]. B) Contact following of locomotion typically occurs during head-to-tail collision and promotes forward migration [12]. C) Cell collision guidance occurs upon lateral collision with a neighboring cell that leads to re-alignment of the colliding cell [15].