Ixodes tick saliva suppresses the keratinocyte cytokine response to TLR2/TLR3 ligands during early exposure to Lyme borreliosis

Abstract

Ixodes hard tick induces skin injury by its sophisticated biting process. Its saliva plays a key role to enable an efficient blood meal that lasts for several days. We hypothesized that this feeding process may also be exploited by pathogens to facilitate their transmission, especially in the context of arthropod-borne diseases. To test this, we used Lyme borreliosis as a model. This bacterial infection is caused by Borrelia burgdorferi sensu lato transmitted by Ixodes. We co-incubated Borrelia with human keratinocytes in the presence of poly (I: C), a dsRNA TLR3 agonist generated by skin injury. This induced a strong cytokine response from human primary keratinocytes that was much greater than that induced by Borrelia alone. OspC, a TLR2/1 agonist and a major surface lipoprotein of Borrelia also amplified the process. Interestingly, tick saliva inhibited cytokine responses by keratinocytes to these TLR agonists. We propose that Borrelia uses the immunoprivileged site produced by tick saliva to facilitate its transmission.

The Essential Role of Tick Salivary Glands and Saliva in Tick Feeding and Pathogen Transmission

“…In particular, chemokines (CXCL8 and CCL2) and AMPs (defensins, cathelicidin, psoriasin, and RNase 7) were down-regulated (Marchal et al, 2011). I. ricinus saliva also inhibited cytokine production by human primary keratinocytes in response to TLR2/TLR3 ligands during Borrelia transmission (Bernard Q. et al, 2016). Nevertheless, the effects of I. scapularis saliva on resident skin cells exposed to Borrelia were found to depend on the cell type (Scholl et al, 2016): tick saliva suppressed the production of the pro-inflammatory mediators IL-6, CXCL8, and TNFα by monocytes, but enhanced the production of CXCL8 and IL-6 by dermal fibroblasts.…”

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

“…Of importance, the immunomodulatory activities of tick saliva have been demonstrated to facilitate pathogen transmission from the tick to the host during the blood meal (11). For example, tick saliva inhibits activation of toll-like receptors 2 and 3 in primary human keratinocyte cell lines, which may facilitate pathogen transmission (12). However, little is known about the ability of tick saliva to modulate the immune system in human skin, since previous studies have been performed only in animal models and in vitro experiments.…”

A joint effort: The interplay between the innate and the adaptive immune system in Lyme arthritis

“…Freshly isolated human PMNs are shown to eradicate spirochetes mostly through antibody‐independent extracellular killing processes such as reactive oxygen species (ROS) production, whereas differentiated monocyte‐derived macrophages ingest the bacteria and kill the spirochetes without the necessity of opsonization . When the tick feeds on a human host, both the bacteria and the tick saliva are released and encounter the accumulating immune cells, influencing the host defense responses …”