Abstract
Lymphatic vessels provide a critical line of communication between peripheral tissues and their draining lymph nodes, which is necessary for robust immune responses against infectious agents. At the same time, lymphatics help shape the nature and kinetics of immune responses to ensure resolution, limit tissue damage, and prevent autoimmune responses. A variety of pathogens have developed strategies to exploit these functions, from multicellular organisms like nematodes to bacteria, viruses, and prions. While lymphatic vessels serve as transport routes for the dissemination of many pathogens, their hypoxic and immune-suppressive environments can provide survival niches for others. Lymphatics can be exploited as perineural niches, for inter-organ distribution among highly motile carrier cells, as effective replicative niches, and as alternative routes in response to therapy. Recent studies have broadened our understanding of lymphatic involvement in pathogenic spread to include a wider range of pathogens, as well as new mechanisms of exploitation, which we summarize here.
Highlights
Lymphatic vessels drain interstitial fluid from most tissues and drive the interstitial fluid flow that carries proteins and macromolecules out of the tissue. This provides the draining lymph nodes (LNs) with a constant stream of information about the specific tissues they drain, including information carried by immune cells that use lymphatic vessels for transport to the LN
Lymphatic endothelial cells (LECs) themselves can directly modulate immune cells, including macrophages, dendritic cells (DCs), and T cells, mostly in roles related to immune regulation [6]
We summarize the strategic advantages of lymphatic dissemination in terms of the migratory immune cells with which lymphatic endothelia have prolonged contact, the immune suppressive environments that can be created, and the advantages of lymphatic vessels, and even lymphatic endothelial cells (LECs) themselves, for replication
Summary
Lymphatic vessels drain interstitial fluid from most tissues and drive the interstitial fluid flow that carries proteins and macromolecules out of the tissue. Lymphatic endothelial cells (LECs) themselves can directly modulate immune cells, including macrophages, DCs, and T cells, mostly in roles related to immune regulation [6] Such regulation may be critical for both resolving effector responses and establishing memory, as well as avoiding autoimmune responses against autoantigens. As controllers of cells and information flow to the LN, and as important sensors and regulators of immunity, lymphatics are central to both orchestrating and regulating immune responses. While these functions evolved to efficiently and appropriately fight infection while preventing autoimmune reactions, many pathogens have developed ways to exploit them for their survival and spread. We outline the pathogenic exploitation of lymphatics of the Peyer’s patches and lymph nodes
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