Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node

The lymphatic system is a network of vessels and a vital part of our immune system. Amongst other things, the lymphatic system carries microbes that have entered the body – for example via to a cut or mosquito bite – to small, oval-shaped organs called lymph nodes. The lymph nodes are packed with immune cells that can be activated to help fight off infections, however certain microbes actually replicate inside the lymph nodes themselves. Lymph nodes protect themselves from these infections by having some pre-armed immune cells that are ready to respond rapidly as soon as an invading microbe is detected. These cells, referred to as innate-like lymphocytes, position themselves at the exposed surfaces of the lymph node – the locations where microbes are most likely to enter the organ. However, it was not known which cues caused these immune cells to assemble and remain at these locations. Zhang et al. now reveal that a signaling molecule called CCL20 attracts the innate-like lymphocytes to the lymph node’s exposed surfaces, while a protein known as CD169 helps to securely attach the innate-like lymphocytes in place. Further experiments then confirmed that positioning the innate-like lymphocytes at this location made mice more able to fight off the disease-causing bacterium Staphyloccus aureus. Unexpectedly, Zhang et al. also found that innate-like lymphocytes can move from the surfaces of lymph node through to the underlying tissue. This unusual migratory behavior might allow the lymphocytes to search a larger area for the infectious microbes, though further studies are needed to test this hypothesis. Future studies are also likely to focus on elucidating how the innate-like lymphocytes recognize different types of invaders, and how their activity keeps the lymph nodes healthy.