For whom the tick "Toll"s

Ixodes scapularis, the blacklegged tick, vectors multiple human pathogens including Borrelia burgdorferi, the agent of Lyme disease. Studies on tick -B. burgdorferi interactions demonstrate that several tick immune pathways including the IMD and JAK-STAT pathways are upregulated in B. burgdorferi-infected ticks. This has been construed as a tick defense response to the human pathogen. There is, however, little evidence to suggest that B. burgdorferi is a pathogen to the tick. While the activation of the IMD pathway has not been shown to clear B. burgdorferi, the activation of the JAK/STAT appears to enhance B. burgdorferi survival in the tick. To further understand tick defense responses in the context of B. burgdorferi, we focused on the Toll pathway. The I. scapularis genome has an intact Toll pathway potentially capable of responding to Gram-positive bacteria. While B. burgdorferi is not a canonical Gram-positive bacterium, we observed the upregulation of several components of the Toll pathway in the B. burgdorferi-infected nymphal ticks. However, RNA-mediated silencing of key components of the Toll pathway did not impact B. burgdorferi survival in the tick. Studies in progress will determine the role of the tick Toll pathway in the context of environmental microbes, including bacteria and fungi that may be detrimental to the tick. Understanding the functional significance of the Toll pathway in the tick may offer new insights into tick biology and reveal new strategies to control ticks in nature.