Healthy skin cells vs. infected skin cells of a patient suffering from Lyme disease.
New insights into the spread of the Lyme disease pathogen: a research group led by the Medical University of Vienna and CeMM has gained new insights into how ticks influence the human immune system in order to introduce pathogens. The study showed 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 Borrelia burgdorferi, the bacterium that causes Lyme disease. The results, published in the journal Nature Communications, provide a possible basis for the development of new vaccination strategies.
The research team – led by postdoctoral researcher Johanna Strobl, project researcher Lisa Kleißl and assistant professor 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 initiate a defensive immune response. However, this does not happen after a tick bite: using skin samples from affected patients and several experimental model systems, the researchers showed that these cells rapidly disappear from the epidermis after contact with tick saliva and migrate to deeper skin layers and lymph vessels. This process is regulated by messenger substances whose receptors (including CCR7 and CXCR4) appear in greater numbers on the cell surface when exposed to tick saliva.
However, the decisive factor is that the function of Langerhans cells changes in the process: the messenger substances in tick saliva induce a so-called tolerogenic state in them. This means that instead of protective, inflammatory defence, they trigger a suppressive, regulatory immune response. Researchers have observed that after contact with tick saliva, Langerhans cells produce increased levels of factors that activate regulatory T cells. These cells slow down immune responses, thereby preventing the effective elimination of pathogens. At the same time, the activation of T-cell types that normally play a role in the early control of bacterial infections is delayed.
Reprogramming the immune response
“Studies of patients with acute Lyme disease confirmed these findings: we found significantly fewer Langerhans cells in the characteristic skin lesions, and these also showed a tolerogenic pattern similar to that observed in model systems,” reports Georg Stary, lead author of the study. “Our results suggest that tick saliva itself plays a decisive role in reprogramming the local immune defence, making it easier for Borrelia bacteria to colonise the body,” adds first author Johanna Strobl. “This may also explain why, unlike many other bacterial diseases, Borrelia burgdorferi infection does not leave behind lasting immunity and why reinfection is possible,” says co-author Lisa Kleißl.
The results provide a possible basis for the development of new vaccination strategies. On the one hand, vaccines specifically targeting Langerhans cells can be further developed with a better understanding of cell migration and functional changes. On the other hand, certain components of tick saliva that target the immune system may become important in the future for both infection prevention and therapeutic applications.
The study is titled “Human epidermal Langerhans cells induce tolerance and hamper T cell function upon tick-borne pathogen transmission” and was published in Nature Communications on 28 November 2025.
DOI: 10.1038/s41467-025-66821-6
Funding:
The work was supported by the Medical Science Fund of the City of Vienna, La Roche-Posay Research Awards Europe, ESCMID research funding, the LEO Foundation and the Austrian The work was supported by the Medical Science Fund of the City of Vienna, La Roche-Posay Research Awards Europe, ESCMID research grants, the LEO Foundation and the Austrian Science Fund (FWF).
Image:
The authors of the study: Georg Stary, Johanna Strobl and Lisa Kleissl.
Source: https://cemm.at/news/detail/tick-saliva-alters-immune-response-of-skin-cells
(C) Lyme Borreliosis Foundation
