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The multiple faces of leukocyte interstitial migration

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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.

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Acknowledgments

We thank Dr. Angelika Rambold for carefully preparing figure illustrations and critically reviewing the manuscript. This work was supported by the Intramural Research Program of NIAID, NIH. T.L. was supported by a long-term fellowship of the Human Frontier Science Program Organization.

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  1. Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Tim Lämmermann & Ronald N. Germain

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  1. Tim Lämmermann
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  2. Ronald N. Germain
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Correspondence to Tim Lämmermann or Ronald N. Germain.

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This article is a contribution to the special issue on New paradigms in leukocyte trafficking, lessons for therapeutics - Guest Editors: F. W. Luscinskas and B. A. Imhof

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Lämmermann, T., Germain, R.N. The multiple faces of leukocyte interstitial migration. Semin Immunopathol 36, 227–251 (2014). https://doi.org/10.1007/s00281-014-0418-8

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