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

Abstract

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 leukocyte 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 h 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 of other pro- (IL-6, IL-12p40, IFN-γ, TNFα) and anti-inflammatory cytokines (IL-4, IL-10, TGFβ) did not differ from normal skin. With longer tick attachment (>24 h), 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 24h of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva.

Ticks, Ixodes scapularis, Feed Repeatedly on White-Footed Mice despite Strong Inflammatory Response: An Expanding Paradigm for Understanding Tick–Host Interactions

“…In addition to the tissue breakdown described earlier, the chemotaxis also led to hyperkeratinization, dermal hyperplasia, and oxidative stress involving ROS ( 17 ). Similar findings regarding neutrophil and macrophage chemoattractants were reported in humans bitten by ticks, Ixodes ricinus ( 28 ). Whether basophils, known to secrete histamine and other cytotoxic molecules ( 29 ) also contribute to the inflammatory response in P. leucopus seems unlikely in view of the small numbers found and mostly confined to blood vessels.…”

Discovery of Exosomes From Tick Saliva and Salivary Glands Reveals Therapeutic Roles for CXCL12 and IL-8 in Wound Healing at the Tick–Human Skin Interface

“…Numerous studies have shown that several tick salivary factors play differential roles to facilitate evasion of host immune responses (Bowman et al, 1997;Nuttall and Labuda, 2004;Bernard et al, 2015;Kotal et al, 2015;Glatz et al, 2017;Nuttall, 2019). We have shown that tick salivary factors elicit differential levels of fibrinogenolysis upon blood feeding on immunocompetent or immunodeficient mice (Vora et al, 2017).…”

Evasins: Tick Salivary Proteins that Inhibit Mammalian Chemokines

“…The same group then showed that tick saliva contains inhibitory activities directed against the chemokines CCL2, CCL3, CCL5, and CCL11 [20]. Importantly, mRNA levels for several of these chemokines are elevated in human skin biopsies from tick bites compared with unaffected skin [21], suggesting that these chemokines are involved in the human reaction to tick bites.…”