Mechanisms and immune consequences of Neutrophil trafficking via lymphatics

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Following injury and infection, the first line of defence is provided by white blood cells termed neutrophils that respond to the presence of invading microbes by emigrating in large numbers from the blood circulation to the tissues. Here, these short-lived professional killers recognize general features shared by all pathogens and kill them by releasing an arsenal of toxic products. The next line of defence is provided by lymphocytes, which respond to the invading microbes by multiplying in the lymph nodes and generating protective antibodies and pathogen specific T cells. Normally this adaptive response relies on the transport of pathogens to the nodes via lymphatic vessels by means of professional sentinels termed dendritic cells which present the pathogen in the appropriate way for lymphocyte activation. Until recently it was thought that the neutrophil and lymphocyte arms of the response (termed innate and adaptive immunity) were essentially independent. However it is now becoming clear that they are not; neutrophils not only act as sentinels carrying pathogens to the lymph nodes but can also communicate with dendritic cells to manipulate antibody and T cell responses. We will investigate how neutrophils enter the lymphatic system and migrate to the lymph nodes, which cells they interact with when they get there and to what extent they can alter conventional immune responses generated by dendritic cells.