In Project 2, researchers will be examining direct immune response mechanisms of the tick, including how the tick identifies a specific pathogen and how it tries to kill that pathogen. Specifically, Dr. Joao Pedra as PI from the University of Maryland School of Medicine will investigate the operation of the tick immune system focusing on the newly discovered atypical Immune Deficiency (IMD) pathway, originally discovered by Pedra. Pedra's lab will work to elucidate how the IMD pathway functions as a molecular rheostat regulating persistence of Borrelia burgdorferi or Anaplasma phagocytophilum in Ixodes scapularis or black-legged ticks. Specific up- and downstream events of “immune cross-talk” between the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway and the IMD pathways will be examined in Projects 1 and 2, further synergizing the studies of vector immunity. This project will leverage contributions from Project 1 defining the JAK/STAT pathway and from the Tick Resources Core for genetic manipulations of tick cells lines and the ticks themselves.

Specific Aims

Microbial detection by Ixodes scapularis ticks through the IMD and JAK/STAT Pathways

Aim 1: Characterize the Ixodes scapularis IMD pathway during pathogen infection.

Aim 2:  Define a molecular crosstalk between the Ixodes scapularis IMD signaling cascade and the JAK/STAT pathway, as there is increasing evidence that Borellia burgdorferi and Anaplasma phagocytophilum may be recognized by multiple pattern recognition receptors.