The cat flea (Ctenocephalides felis) immune deficiency signaling pathway regulates Rickettsia typhi infection
JournalInfection and Immunity
PublisherAmerican Society for Microbiology
MetadataShow full item record
AbstractRickettsia species are obligate intracellular bacteria with both conserved and lineage-specific strategies for invading and surviving within eukaryotic cells. One variable component of Rickettsia 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 fleaborne Rickettsia typhi, 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 R. typhi biology in flea vectors that, importantly, do not suffer lethality due to R. typhi infection. To address if fleas combat rickettsial infection, we characterized the cat flea (Ctenocephalides felis) innate immune response to R. typhi. Initially, we determined that R. typhi infects Drosophila cells and increases antimicrobial peptide (AMP) gene expression, indicating immune pathway activation. While bioinformatics analysis of the C. felis transcriptome identified homologs to all of the Drosophila immune deficiency (IMD) and Toll pathway components, an AMP gene expression profile in Drosophila cells indicated IMD pathway activation upon rickettsial infection. Accordingly, we assessed R. typhi-mediated flea IMD pathway activation in vivo using small interfering RNA (siRNA)-mediated knockdown. Knockdown of Relish and Imd increased R. typhi infection levels, implicating the IMD pathway as a critical regulator of R. typhi burden in C. felis. These data suggest that targeting the IMD pathway could minimize the spread of R. typhi, and potentially other human pathogens, vectored by fleas. Copyright 2017 American Society for Microbiology.
SponsorsThis work was supported with funds from National Institutes of Health/National Institute of Allergy and Infectious Diseases grants (R01AI017828 and R01AI126853 and R21AI26108, NIH/NIAID grant T32AI095190 (Signaling Pathways in Innate Immunity), NIH/NIAID grants T32AI095190 (Signaling Pathways in Innate Immunity) and T32AI007540 (Infection and Immunity).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85039561615&doi=10.1128%2fIAI.00562-17&partnerID=40&md5=6da9b41d92f53cf1080f95f2b47e9e89; http://hdl.handle.net/10713/9440
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