© 2019 by Tick Immunity. Created by Valerie Hoy and Samantha Watters.

ABOUT OUR WORK

Globally, the rate of tick-borne infection is severely underappreciated and underestimated.  A few decades ago, discovery of “Lyme disease” in the Lyme County in Connecticut spurred unprecedented public attention to tick-borne disease.  Soon after, the Centers for Disease Control and Prevention (CDC) initiated nation-wide surveillance, and newly revised estimates suggest that there are over 300,000 new cases of Lyme disease occurring every year in the United States.  In addition, more than ten newly recognized tick-borne pathogens and diseases were identified in the Western Hemisphere during the last two decades.  Therefore, there is an urgent and unmet need to study tick-borne infection.  Understanding how ticks recognize and suppress invading microbes is the study of Tick Immunity or tick immune response, and this knowledge could be used to develop future prevention and treatment strategies to ultimately eliminate these pathogens and cure diseases like Lyme disease.

To facilitate this need and meet the concerns of a growing public health issue, this team is working under a PO1 multi-project grant awarded by the National Institute of Allergy and Infectious Diseases (NIAID), under the National Institutes of Health (NIH).

 

The new tick program is the first-of-its-kind in tick-borne illness research, and has three major research components centered around tick immune response, as well as a Tick Resource Core, each with a different institution at the helm. The central goal is to generate fundamental knowledge of tick immunobiology, particularly to understand the molecular mechanisms by which the Ixodes scapularis or black-legged tick's immune system recognizes invading microbes, interfaces with resident gut microbiota, and ultimately impacts pathogen persistence. The program is studying the most common tick that carries the two most prevalent tick-borne pathogens due to their impact on human health and their unique characteristics on a cellular level. Borrelia burgdorferi is the pathogen that causes Lyme disease, and Anaplasma phagocytophilum causes Anaplasmosis.

 

Dr. Utpal Pal of the University of Maryland, College Park, will be handling the Administrative Core for the program and helping advise and coordinate all projects. Pal and his team will also be leading research on Project 1 in indirect immune response mechanisms in ticks that carry pathogens contributing to Lyme disease and other illnesses. Indirect immune response was a phenomena that Pal discovered originally in his lab and is a mechanism by which the tick feeding on a mammal host, most commonly mice or deer, recognizes some sort of illness in the blood as it is being ingested, triggering a non-specific line of immune defense to try to kill whatever is there.

Dr. Joao Pedra as Principal Investigator from the University of Maryland School of Medicine will be examining direct immune response mechanisms of the tick in research for Project 2, which include how the tick identifies a specific pathogen and what tactics it employs to try and kill that pathogen.

Dr. Erol Fikrig as Principal Investigator from Yale University will be examining how microbiota or gut bacteria in the tick interacts with immune responses the tick uses to try and kill pathogens in the blood it ingests in research for Project 3.

 

Dr. Ulrike Munderloh from University of Minnesota will serve as Technical Core Lead for the program, providing additional technical support including protocols and tools needed to facilitate this research as Director of the Tick Resources Core.

The full program title of the Tick Immunity Project is Tick Immune Signaling, Microbiota, and Acquisition of Borrelia burgdorferi and Anaplasma phagocytophilum, NIH Project Number 1P01AI138949-01.

Click on Each Project to Learn More

Scientific review of progress; annual Symposium
Centralized oversight
Microbial recognition by the immune deficiency pathway of ticks
Ixodes-vector-based tools; Cell lines and ticks, naive and genetically-modified
Cross-species immunity signals impacting persistence of tick-borne pathogens
Interplay between the tick microbiota, immune signaling, and pathogen infection

Overall Specific Aims

Aim 1: Develop and operate a Tick Core. The core will provide necessary research reagents to all projects, including ticks, Ixodes scapularis cell lines and tick cells modified via Clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 or reporter tags). The Core will also instruct personnel from all projects on how to cultivate, prepare, or manipulate tick cells and ticks.

Aim 2: Determine how mammalian factors present in tick-ingested blood meal stimulate multiple cross-species immunity signaling pathways, impacting persistence of diverse pathogens.

Aim 3: Investigate molecular basis of microbial detection and signaling relays by multiple immune pathways in ticks.

Aim 4: Examine interactions between tick gut immunome and gut microbiota and how these events impact persistence of tick-borne pathogens.