The Cat Flea (Ctenocephalides felis) Immune Deficiency Signaling Pathway Regulates Rickettsia typhi Infection.

species are obligate intracellular bacteria with both conserved and lineage-specific strategies for invading and surviving within eukaryotic cells. One variable component of biology involves arthropod vectors: for instance, typhus group rickettsiae are principally vectored by insects (i.e., lice and fleas), whereas spotted fever group rickettsiae are exclusively vectored by ticks. For flea-borne , the etiological agent of murine typhus, research on vertebrate host biology is facilitated using cell lines and animal models. However, due to the lack of any stable flea cell line or a published flea genome sequence, little is known regarding biology in flea vectors that, importantly, do not suffer lethality due to infection. To address if fleas combat rickettsial infection, we characterized the cat flea () innate immune response to Initially, we determined that infects cells and increases antimicrobial peptide (AMP) gene expression, indicating immune pathway activation. While bioinformatics analysis of the transcriptome identified homologs to all of the immune deficiency (IMD) and Toll pathway components, an AMP gene expression profile in cells indicated IMD pathway activation upon rickettsial infection. Accordingly, we assessed -mediated flea IMD pathway activation using small interfering RNA (siRNA)-mediated knockdown. Knockdown of and increased infection levels, implicating the IMD pathway as a critical regulator of burden in These data suggest that targeting the IMD pathway could minimize the spread of , and potentially other human pathogens, vectored by fleas.