WHY TICK IMMUNITY?
Did you know that ticks don’t want to be carrying pathogens any more than we do? Their immune systems have actually developed sophisticated methods of sensing and fighting pathogens like Borrelia burgdorferi and Anaplasma phagocytophilum already. So the question becomes: What can we learn from tick immunity? That is the reasoning behind the study of tick immunobiology or tick immune response, and the basis for the Tick Immunity research program. An understanding of the mechanisms that contribute to tick immunity, including the identification of pathogens in the blood meal a tick ingests, the different defense tactics or immune responses deployed to kill these pathogens, and ultimately how these pathogens continue to persist may hold the key to the development of vaccines and treatments, as well as the eradication of these pathogens and diseases like Lyme disease and Anaplasmosis.
The Basis for Our Work
Tick Immunity is centered on the study of tick immunobiology, looking at the Ixodes scapularis or black-legged tick's immune system and how it recognizes invading microbes, interacts with tick gut microbiota, and ultimately impacts the persistence of the pathogens that cause two major tick-borne diseases, Lyme disease and Anaplasmosis. The black-legged tick is the most common tick to carry these tick-borne pathogens, Borrelia burgdorferi (Lyme disease) and Anaplasma phagocytophilum (Anaplasmosis). The public health impact and burden of these diseases is a substantial and growing public health concern, but the field of tick immune response has been largely understudied. The following outline the basis of our research projects:
Ticks are ancient and unique disease vectors, but largely understudied. Ticks are completely distinct from mosquitoes and other commonly studied insect vectors, and originated several hundreds of millions of years earlier. Borrelia burgdorferi was found in the 2012 discovery of the 5,300-year-old Copper age remains of “The Iceman,” and again in 2014, in a tick that dates back 20 million years. This means that the properties of ticks can truly only be understood from studies directly in ticks, and this research is largely lacking. Due to increasing global awareness, the U.S. Senate recently passed the 21st Century Cures Act that prioritizes research on tick-borne diseases, including the development of novel vaccines and treatment strategies.
Ticks transmit prevalent and atypical bacterial infections causing illnesses like Lyme disease and Anaplasmosis. Approximately 95 percent of reported cases of vector-borne disease are actually associated with ticks, making these the most medically important group of arthropods in the U.S. There are at least 15 tick-borne diseases known to occur in the U.S. alone, and the majority of these infections are caused by bacterial pathogens, including agents of Lyme disease. Mosquito-borne illnesses have garnered more attention historically because of the higher mortality rates, but morbidity and quality of life, as well as the overall prevalence of tick-borne illnesses, make the public health burden even more substantial.
Ixodes tick immune responses against pathogens are regulated by cell-instrinsic and extrinsic factors that are interlinked. Recent availability of tick genome sequencing data and comparative analysis has established that ticks lack many key orthologs of major immunity pathways like the Janus kinase/signal transducer and activators of transcription (JAK/STAT) or the Immune Deficiency (IMD) pathway, and yet these pathways remain functional. This may be attributed to the existence of undiscovered pathways or their interactions and cross-talk, as well as their connections to the microbiota in the tick's gut. The complexity, inter-relatedness, and overlapping effects on the same pathogens for these immune pathways makes it essential to have an interdisciplinary team to study these phenomena.
New emerging concepts of vector immunity need farther study, including direct and indirect ways of pathogen recognition and defense responses. Recently and newly discovered pathways such as the IMD pathway by Dr. Joao Pedra or the concept of indirect immune response by Dr. Utpal Pal in ticks require farther study. Evolving millions of years earlier than other vectors, these immune responses are highly sophisticated and complex, and hold keys to the expansion of treatment and prevention measures across the wide array of tick-borne illnesses.
The depth of the damage, the seriousness of what ticks can do, has not been appreciated as it should. Mosquitoes get most of the attention. But the genetic difference between ticks and mosquitoes is like the difference between humans and—not even mice, but fish. They are widely different. So the knowledge we have from studying mosquitoes isn’t applicable to ticks. It’s important that we focus more on using ticks and tick-borne diseases in experimental research. And I think this will help us understand how the infection functions and is transmitted by ticks. Our research will look at how ticks kill the pathogens, because if you disable a tick’s immune system, Borrelia skyrockets. So ticks actually suppress infection. If we know how they do this, we can turn the tables and use that information to develop vaccines.
Dr. Utpal Pal, Principal Investigator
University of Maryland, College Park