Tuning immunity through tissue mechanotransduction.

Immune responses are governed by signals from the tissue microenvironment, and in addition to biochemical signals, mechanical cues and forces arising from the tissue, its extracellular matrix and its constituent cells shape immune cell function. Indeed, changes in biophysical properties of tissue alter the mechanical signals experienced by cells in many disease conditions, in inflammatory states and in the context of ageing. These mechanical cues are converted into biochemical signals through the process of mechanotransduction, and multiple pathways of mechanotransduction have been identified in immune cells. Such pathways impact important cellular functions including cell activation, cytokine production, metabolism, proliferation and trafficking. Changes in tissue mechanics may also represent a new form of 'danger signal' that alerts the innate and adaptive immune systems to the possibility of injury or infection. Tissue mechanics can change temporally during an infection or inflammatory response, offering a novel layer of dynamic immune regulation. Here, we review the emerging field of mechanoimmunology, focusing on how mechanical cues at the scale of the tissue environment regulate immune cell behaviours to initiate, propagate and resolve the immune response.

Host-Specific Activation of Entomopathogenic Nematode Infective Juveniles.

Entomopathogenic nematodes (EPNs) are potent insect parasites and have been used for pest control in agriculture. Despite the complexity of the EPN infection process, hosts are typically killed within 5 days of initial infection. When free-living infective juveniles (IJs) infect a host, they release their bacterial symbiont, secrete toxic products, and undergo notable morphological changes. Collectively, this process is referred to as "activation" and represents the point in a nematode's life cycle when it becomes actively parasitic. The effect of different host tissues and IJ age on activation, and how activation itself is related to virulence, are not well understood. Here, we employed a recently developed bioassay, which quantifies IJ activation, as a tool to address these matters. Appreciating that activation is a key part of the EPN infection process, we hypothesized that activation would positively correlate to virulence. Using the EPNs Steinernema carpocapsae and S. feltiae we found that EPN activation is host-specific and influenced by infective juvenile age. Additionally, our data suggest that activation has a context-dependent influence on virulence and could be predictive of virulence in some cases such as when IJ activation is especially low.