Role for Mechanotransduction in Macrophage and Dendritic Cell Immunobiology

Abstract

Tissue homeostasis is not only controlled by biochemical signals but also through mechanical forces that act on cells. Yet, while it has long been known that biochemical signals have profound effects on cell biology, the importance of mechanical forces has only been recognized much more recently. The types of mechanical stress that cells experience include stretch, compression, and shear stress, which are mainly induced by the extracellular matrix, cell-cell contacts, and fluid flow. Importantly, macroscale tissue deformation through stretch or compression also affects cellular function.Immune cells such as macrophages and dendritic cells are present in almost all peripheral tissues, and monocytes populate the vasculature throughout the body. These cells are unique in the sense that they are subject to a large variety of different mechanical environments, and it is therefore not surprising that key immune effector functions are altered by mechanical stimuli. In this chapter, we describe the different types of mechanical signals that cells encounter within the body and review the current knowledge on the role of mechanical signals in regulating macrophage, monocyte, and dendritic cell function.

The mechanics of myeloid cells

“…These results confirm the data obtained from the optical stretcher [Ekpenyong et al., ]. This process, in which a physical force elicits a functional response, is an example of mechanotransduction [Ekpenyong et al., ; Mennens et al., ; Novikova et al., ].…”

Cyclic Stretch Negatively Regulates IL-1β Secretion Through the Inhibition of NLRP3 Inflammasome Activation by Attenuating the AMP Kinase Pathway

“…Our results indicate that cyclic stretch plays an important role in preventing excessive inflammasome activation in mechanical environmental tissues ( Oya et al, 2013 ; Mennens et al, 2017 ), such as the lungs, heart, arterial wall, and periodontal ligament, in which the infiltration of large numbers of macrophages derived from peripheral blood monocytes occurs during the processes of inflammation and tissue repair. Of these tissues, the periodontal ligament, which is located between the tooth root and its surrounding bone ( Bartold, 2012 ), is subjected to mechanical stimuli, including cyclic stretch, from normal mastication.…”

“…Cells encounter many dynamic mechanical forces, e.g., shear stress from fluid flow, mechanical loading in bone or cartilage tissue, or cyclic stretch from several tissues such as the periodontal ligament, lung, heart, and vasculature. Cells that are surrounded by an extracellular matrix (ECM) also encounter static mechanical forces with various physical properties, such as stiffness and the topography of the ECM ( McWhorter et al, 2015 ; Mennens et al, 2017 ).…”

Mechanical regulation of macrophage function - cyclic tensile force inhibits NLRP3 inflammasome-dependent IL-1β secretion in murine macrophages

“…However, in the case of tissue injury or infection, monocytes derived from bone marrow circulating in peripheral blood migrate to the affected tissue, differentiate into macrophages, and are involved in the inflammatory response [23]. The cellular functions of tissue-resident macrophages and peripheral blood-derived macrophages are affected by the tissue-specific microenvironment, which can create many types of mechanical stress on cells [24, 25]. Stiffness and topography, which are mechanical properties of the extracellular matrix, regulate the differentiation, proliferation, and function of macrophages.…”