Characterization of the early local immune response to Ixodes ricinus tick bites in human skin

Little is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick‐host interaction. We examined the expression of chemokines, cytokines and leucocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick‐bite skin lesions (<24 hours of tick attachment) were characterized by a predominance of macrophages and dendritic cells, elevated mRNA levels of macrophage chemoattractants (CCL2, CCL3, CCL4) and neutrophil chemoattractants (CXCL1, CXCL8), of the pro‐inflammatory cytokine, IL‐1β, and the anti‐inflammatory cytokine, IL‐5. In contrast, the numbers of lymphocytes and mRNA levels of lymphocyte cell markers (CD4, CD8, CD19), lymphocyte chemoattractants (CXCL9, CXCL10, CXCL11, CXCL13, CCL1, CCL22), dendritic cell chemoattractants (CCL20), and other pro‐ (IL‐6, IL‐12p40, IFN‐γ, TNF‐α) and anti‐inflammatory cytokines (IL‐4, IL‐10, TGF‐β) did not differ from normal skin. With longer tick attachment (>24 hours), the numbers of innate immune cells and mediators (not significantly) declined, whereas the numbers of lymphocytes (not significantly) increased. Natural tick bites by Ixodes ricinus ticks initially elicit a strong local innate immune response in human skin. Beyond 24 hours of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva.