The multiple faces of leukocyte interstitial migration

Abstract

Spatiotemporal control of leukocyte dynamics within tissues is critical for successful innate and adaptive immune responses. Homeostatic trafficking and coordinated infiltration into and within sites of inflammation and infection rely on signaling in response to extracellular cues that in turn controls a variety of intracellular protein networks regulating leukocyte motility, migration, chemotaxis, positioning, and cell–cell interaction. In contrast to mesenchymal cells, leukocytes migrate in an amoeboid fashion by rapid cycles of actin polymerization and actomyosin contraction, and their migration in tissues is generally referred to as low adhesive and nonproteolytic. The interplay of actin network expansion, contraction, and adhesion shapes the exact mode of amoeboid migration, and in this review, we explore how leukocyte subsets potentially harness the same basic biomechanical mechanisms in a cell-type-specific manner. Most of our detailed understanding of these processes derives from in vitro migration studies in three-dimensional gels and confined spaces that mimic geometrical aspects of physiological tissues. We summarize these in vitro results and then critically compare them to data from intravital imaging of leukocyte interstitial migration in mouse tissues. We outline the technical challenges of obtaining conclusive mechanistic results from intravital studies, discuss leukocyte migration strategies in vivo, and present examples of mode switching during physiological interstitial migration. These findings are also placed in the context of leukocyte migration defects in primary immunodeficiencies. This overview of both in vitro and in vivo studies highlights recent progress in understanding the molecular and biophysical mechanisms that shape robust leukocyte migration responses in physiologically complex and heterogeneous environments.

HIV-1 reprograms the migration of macrophages

“…Finally, the increased adhesion is certainly the result of bigger and more stable podosomes, as they constitute the unique adhesion structures of macrophages. 26 Increased cell adhesion correlates with decreased 2D migration, 77 suggesting that, by acting on podosomes, HIV-1 affects both 2D motility and 3D mesenchymal migration. To our knowledge, HIV-1 is the first pathogen able to modify the structure and function of constitutive podosomes in macrophages.…”

Microtubules in 3D cell motility

“…However, soft collagen-rich matrices are considered to mimic well multiple types of in vivo tissue environments (Doyle et al, 2009;. Early research using soft collagen gels and ex vivo cultures led to the definition of two main 3D motility modes: (i) amoeboid cell migration, as seen in leukocytes (Lam and Huttenlocher, 2013;Lammermann and Germain, 2014) and (ii) mesenchymal cell migration, found in fibroblasts, invasive cancer cells and many developmental precursors, especially during EMT (Friedl and Wolf, 2010;Lim and Thiery, 2012). Amoeboid migration is characteristic for rounded cells with relatively low ECM adhesion and relatively high Rho-driven contractility, whereas mesenchymal migration depends on cell elongation associated with relatively high ECM adhesion and Rac1-driven protrusion (Friedl and Wolf, 2010).…”

Aquaporins in Infection and Inflammation

“…by matrix metalloproteases (MMPs) [62]. The cells can transition between these two modes of migration in 3D matrices [63,64]. Multicellular migration is not completely separated from single cell migration.…”