Abstract Background: Bed bugs (Hemiptera: Cimicidae) are a widely distributed, obligately blood-feeding insect, but they have never been linked to pathogen transmission in humans. Most other hematophagous insects that frequently bite humans transmit pathogens, and it is unclear why bed bugs do not. One hypothesis is that bed bugs have evolved a highly robust immune system because their mating system, traumatic insemination, exposes females to consistent wounding and bacterial infections.