OVERALL - Abstract The proposed Program Project (P01), entitled ?Tick Immune Signaling, Microbiota, and Acquisition of Borrelia burgdorferi and Anaplasma phagocytophilum? aims to understand the molecular mechanisms by which the Ixodes tick immune system recognizes invading microbes, interfaces with resident gut microbiota, and impact pathogen persistence. We discovered two unorthodox tick immune cascades that are (a) involved in microbial recognition by an indirect ?cross-kingdom? circuit triggered by a mammalian cytokine acquired in the vector blood meal, or (b) by a direct induction by specific bacterial lipids through an atypical immunodeficiency pathway. We also established that (c) interactions between tick gut microbiota and invading pathogens shape vector physiology and immunity, ultimately impacting the ability of ticks to acquire B. burgdorferi or A. phagocytophilum. Building on these paradigms and by combining the expertise and resources from four institutions with impressive history of research involving tick-borne infections, we will determine how discrete Ixodes tick immune pathways, either independently or synergistically, influence the entry and persistence of two major pathogens, B. burgdorferi and A. phagocytophilum. These microbes constitute the focus of our proposal due to their diverse structural and genetic features, their different lifestyles - either extracellular or intracellular - and the fact that they are responsible for the most prevalent tick-borne infections in the United States and many parts of Europe. This Program Project Grant leverages specific assays, tools and methodologies developed by our laboratories, who have a long history of productive collaboration, and which will be supported by an Administrative Core, and a Tick Resource Core whereby organisms and cell lines will be shared. The proposed aims to achieve the goals of this P01 are 1) Develop a Tick Core that provides the research reagents to all projects and to scientific community; 2) Determine how mammalian factors present in tick blood meal stimulate multiple cross-species immunity signaling pathways impacting persistence of diverse pathogens; 3) Investigate molecular basis of microbial detection in ticks via signaling relays and crosstalk by multiple immune pathways; 4) Examine interactions between tick immunome and gut microbiota and how these events impact persistence of tick-borne pathogens. Altogether, this proposal will increase our fundamental understanding of how tick immune signaling pathways operate and interface with the gut microbiota to influence the ability of diverse tick-borne pathogens to persist in the vector and subsequently infect the vertebrate host. The outreach activities generated by sharing the research data, and resources to the scientific community will plant new seeds of innovative research furthering our knowledge of tick-borne infections. Finally, with the technical and conceptual breakthroughs expected, the P01 will entice a new generation of scientists to be engaged and advance this important, yet neglected field of scientific research.

Public Health Relevance

OVERALL ? Narrative The blacklegged tick, Ixodes scapularis, is a major vector of Borrelia burgdorferi, the agent of Lyme disease and Anaplasma phagocytophilum, the agent of human Anaplasmosis, causing most prevalent vector-borne diseases in the United States and many parts of Europe. This Program Project Grant will provide a detailed understanding of the role of tick immune responses in coordination with the tick gut microbiota, and how they interface, crosstalk, and impact survival of these pathogens in the tick. Since pathogen survival in the tick is a critical determinant of infection prevalence in endemic areas, this collaborative research effort will facilitate future development of new strategies to control the prevalence and spread of multiple tick-borne infections.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1)
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Costero-Saint Denis, Adriana
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University of Maryland College Park
Veterinary Sciences
Earth Sciences/Resources
College Park
United States
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Shaw, Dana K; Tate, Ann T; Schneider, David S et al. (2018) Vector Immunity and Evolutionary Ecology: The Harmonious Dissonance. Trends Immunol 39:862-873
McClure Carroll, Erin E; Wang, Xiaowei; Shaw, Dana K et al. (2018) p47 licenses activation of the immune deficiency pathway in the tick Ixodes scapularis. Proc Natl Acad Sci U S A :