In Project 3, researchers will examine how gut bacteria or microbiota in ticks interacts with their immune responses to kill pathogens in the blood they ingest. Dr. Erol Fikrig as PI from Yale University will explore interactions between the tick immunome and the gut microbiota, and how they maintain bacterial homeostasis and impact the infection of Ixodes scapularis or black-legged ticks by the Borrelia burgdorferi or Anaplasma phagocytophilum pathogens. This will closely align with Project 1 and study of the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway, Project 2 and the Immune Deficiency (IMD) pathway, and the Tick Resources Core, including microbiome tools, membrane feeders, and bacterial reconstitution studies. The goal of these studies is to look at the whole picture of how these pathways interact with the entire microbiome, as well as specific gut bacteria through reconstitution studies that might interface with the specific pathways of the tick gut to affect overall pathogen burden on the tick. 

Specific Aims

Tick gut immune-gut microbiota interactions in the context of tick-borne pathogens

Aim 1: Define the interactions between tick gut immune pathways and tick gut microbiota. The goal of experiments are to determine 1.1) the impact of dysbiosis on IFNg-JAK/STAT and IMD signaling pathways and 1.2) the impact of IFNg-JAK/STAT and IMD signaling on tick gut microbiota.

Aim 2: Determine the impact of specific microbiota on immune signaling and Borrelia burgdorferi colonization and Anaplasma phagocytophilum infection. The goal of these studies to define 2.1) specific bacterial components that modulate the IFNg-JAK/STAT and IMD Immune pathways and 2.2) specific bacteria that modulate the IFNg-JAK/STAT and IMD immune pathways.