When Ixodes scapularis ticks are colonized by Borrelia burgdorferi (causative agent of Lyme disease) or Anaplasma phagocytophilum (causative agent of granulocytic anaplasmosis), the IRE1α receptor undergoes self-phosphorylation and pairs with TNF receptor associated factor 2 (TRAF2) to activate the IMD pathway (20). Here, TRAF2 is linked to Lyme disease.