The human body and head louse are ectoparasites of humans for thousands of years. Although both body and head lice belong to a single species, Pediculus humanus, only body lice are known to transmit several bacterial diseases. This different vector competence is assumed to be due to their different immune responses. Here, the immune reactions in the alimentary canal were investigated in both two louse subspecies following oral challenge of Escherichia coli as a model gram-negative bacteria. In propagation assay, head lice suppressed the proliferation of E. coli in their epithelial cells effectively at the early stage of infection, resulting in gradual reduction of E. coli number in gut tissues. In contrast, the number of E. coli steadily increased in gut tissues of body lice. No apparent alteration of transcription was observed following E. coli challenge in three important genes for the humoral immune responses, PGRP as a recognition gene and defensin1 and 2 as effector genes. Nevertheless, the basal transcription levels of these genes were higher in the gut tissues of head lice than body lice. Considering that there is no cellular immune reactions in gut tissues, these findings suggest that the higher constitutive transcription levels of major immune genes in head lice can contribute to their initial defense and immune capacity against intestinal bacterial infection.