Affiliation:
1. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
2. Department of Biology, West Virginia University, Morgantown, West Virginia, USA
Abstract
ABSTRACT
Rickettsia
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 flea-borne
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.
Funder
HHS | NIH | National Institute of Allergy and Infectious Diseases
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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