In Project 1, researchers will examine the indirect immune response mechanisms in ticks as they try to kill pathogens like Borrelia burgdorferi and Anaplasma phagocytophilum. Originally discovered by the PI for Project 1 and the Lead PI for Tick Immunity, Dr. Utpal Pal of the University of Maryland, indirect immune response is a mechanism by which a tick feeding on a mammal host recognizes something wrong with the blood meal being ingested, triggering non-specific immune defense measures to kill whatever pathogens are there. The goal is to characterize how “cross-kingdom” immune circuits, triggered by specific mammalian cytokines or proteins like IFNγ acquired in the blood meal and orchestrated by the Janus kinase/signal transducer and activators of transcription (JAK/STAT) or other immune pathways like the Immune Deficiency (IMD) pathway, enable efficient recognition of the pathogen and its control in ticks. Understanding these pathways can lead to greater knowledge for development of treatments and vaccines. Pal served on the Tick Working Group Subcommittee for Vaccines and Therapeutics with DHHS.

Specific Aims

Cross-species immunity signals impacting persistence of tick-borne pathogens

Aim 1: Define how cross-species IFNγ signaling boosts tick borreliocidal activity. The goal of these studies is to systematically dissect molecular details of the newly recognized IFNγ signaling pathway in ticks.

Aim 2: Assess how cross-species IFNγ signaling interfaces with other immune pathways and impacts additional pathogens. Our current goals are to determine how the incoming blood meal components impact persistence of diverse pathogens through a holistic immune response.