How tick saliva reprograms the skin’s immune defenses

A research team led by the Medical University of Vienna has gained new insights into how ticks influence the human immune system in order to introduce pathogens. The study shows that the saliva of Ixodes ricinus - the most common tick species in Central Europe - plays a central role in altering the immune response of skin cells, thereby facilitating the transmission of the Lyme disease pathogen Borrelia burgdorferi. The findings, published in the journal Nature Communications, provide a possible basis for the development of new vaccination strategies.

The research team led by Johanna Strobl, Lisa Kleiβl and Georg Stary (all from the Department of Dermatology at MedUni Vienna and CeMM) focused on so-called Langerhans cells. These specialised immune cells are located in the epidermis and are normally the first to recognise pathogens and trigger a defensive response. This is not the case after a tick bite: using skin samples from affected patients and several experimental model systems, the scientists were able to show that these cells rapidly disappear from the epidermis after contact with tick saliva and migrate into deeper skin layers and lymph vessels. This process is controlled by messenger substances whose receptors (including CCR7 and CXCR4) appear more frequently on the cell surface due to the tick saliva.

Yet, the decisive factor is how the function of the Langerhans cells changes in the process: the messenger substances in tick saliva put them into a so-called tolerogenic state. This means that instead of a protective, pro-inflammatory defence reaction, the cells trigger a suppressive, regulatory immune response. The researchers observed that, after contact with tick saliva, Langerhans cells increasingly produce factors that activate regulatory T cells. These cells slow down immune responses, thereby preventing effective combat against pathogens. At the same time, the activation of those T cell types that are usually involved in the early control of bacterial infections failed to occur.

Immune response is reprogrammed

"Our investigations of patients with acute Lyme disease confirmed these results: we found significantly fewer Langerhans cells in the characteristic skin lesions, which also showed a similar tolerogenic pattern to that seen in the model systems," reports study leader Georg Stary from the research department.

Our results suggest that tick saliva itself plays a decisive role in reprogramming the local immune defence so that Borrelia bacteria can colonise the body more easily."

Johanna Strobl, first author 

"This could also explain why infection with Borrelia burgdorferi - unlike many other bacterial diseases - often does not leave lasting immunity and repeated infections are possible," says co-first author Lisa Kleiβl.

The findings provide a possible basis for the development of new vaccination strategies. On the one hand, vaccines that specifically target Langerhans cells could be further improved through a better understanding of their migration and functional changes. On the other hand, individual components of tick saliva that specifically target the immune system could become relevant in the future for both the prevention of infections and therapeutic applications.