Dataset Information

Evaluation of the murine immune response to Xenopsylla cheopis flea saliva and its effect on transmission of Yersinia pestis.

ABSTRACT:

Background/aims

Arthropod-borne pathogens are transmitted into a unique intradermal microenvironment that includes the saliva of their vectors. Immunomodulatory factors in the saliva can enhance infectivity; however, in some cases the immune response that develops to saliva from prior uninfected bites can inhibit infectivity. Most rodent reservoirs of Yersinia pestis experience fleabites regularly, but the effect this has on the dynamics of flea-borne transmission of plague has never been investigated. We examined the innate and acquired immune response of mice to bites of Xenopsylla cheopis and its effects on Y. pestis transmission and disease progression in both naïve mice and mice chronically exposed to flea bites.

Methods/principal findings

The immune response of C57BL/6 mice to uninfected flea bites was characterized by flow cytometry, histology, and antibody detection methods. In naïve mice, flea bites induced mild inflammation with limited recruitment of neutrophils and macrophages to the bite site. Infectivity and host response in naïve mice exposed to flea bites followed immediately by intradermal injection of Y. pestis did not differ from that of mice infected with Y. pestis without prior flea feeding. With prolonged exposure, an IgG1 antibody response primarily directed to the predominant component of flea saliva, a family of 36-45 kDa phosphatase-like proteins, occurred in both laboratory mice and wild rats naturally exposed to X. cheopis, but a hypersensitivity response never developed. The incidence and progression of terminal plague following challenge by infective blocked fleas were equivalent in naïve mice and mice sensitized to flea saliva by repeated exposure to flea bites over a 10-week period.

Conclusions

Unlike what is observed with many other blood-feeding arthropods, the murine immune response to X. cheopis saliva is mild and continued exposure to flea bites leads more to tolerance than to hypersensitivity. The immune response to flea saliva had no detectable effect on Y. pestis transmission or plague pathogenesis in mice.

SUBMITTER: Bosio CF

PROVIDER: S-EPMC4177749 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

Evaluation of the murine immune response to Xenopsylla cheopis flea saliva and its effect on transmission of Yersinia pestis.

Bosio Christopher F CF Viall Austin K AK Jarrett Clayton O CO Gardner Donald D Rood Michael P MP Hinnebusch B Joseph BJ

PLoS neglected tropical diseases 20140925 9

<h4>Background/aims</h4>Arthropod-borne pathogens are transmitted into a unique intradermal microenvironment that includes the saliva of their vectors. Immunomodulatory factors in the saliva can enhance infectivity; however, in some cases the immune response that develops to saliva from prior uninfected bites can inhibit infectivity. Most rodent reservoirs of Yersinia pestis experience fleabites regularly, but the effect this has on the dynamics of flea-borne transmission of plague has never bee ...[more]

PMID: 25255317

Similar Datasets

Project description:Yersinia pestis, the causative agent of plague, is a highly lethal pathogen transmitted by the bite of infected fleas. Once ingested by a flea, Y. pestis establish a replicative niche in the gut and produce a biofilm that promotes foregut colonization and transmission. The rat flea Xenopsylla cheopis is an important vector to several zoonotic bacterial pathogens including Y. pestis. Some fleas naturally clear themselves of infection; however, the physiological and immunological mechanisms by which this occurs are largely uncharacterized. To address this, RNA was extracted, sequenced, and distinct transcript profiles were assembled de novo from X. cheopis digestive tracts isolated from fleas that were either: 1) not fed for 5 days; 2) fed sterile blood; or 3) fed blood containing ~5x108 CFU/ml Y. pestis KIM6+. Analysis and comparison of the transcript profiles resulted in identification of 23 annotated (and 11 unknown or uncharacterized) digestive tract transcripts that comprise the early transcriptional response of the rat flea gut to infection with Y. pestis. The data indicate that production of antimicrobial peptides regulated by the immune-deficiency pathway (IMD) is the primary flea immune response to infection with Y. pestis. The remaining infection-responsive transcripts, not obviously associated with the immune response, were involved in at least one of 3 physiological themes: 1) alterations to chemosensation and gut peristalsis; 2) modification of digestion and metabolism; and 3) production of chitin-binding proteins (peritrophins). Despite producing several peritrophin transcripts shortly after feeding, including a subset that were infection-responsive, no thick peritrophic membrane was detectable by histochemistry or electron microscopy of rat flea guts for the first 24 hours following blood-feeding. Here we discuss the physiological implications of rat flea infection-responsive transcripts, the function of X. cheopis peritrophins, and the mechanisms by which Y. pestis may be cleared from the flea gut.

Project description:Over the last 20 years, advances in sequencing technologies paired with biochemical and structural studies have shed light on the unique pharmacological arsenal produced by the salivary glands of hematophagous arthropods that can target host hemostasis and immune response, favoring blood acquisition and, in several cases, enhancing pathogen transmission. Here we provide a deeper insight into Xenopsylla cheopis salivary gland contents pairing transcriptomic and proteomic approaches. Sequencing of 99 pairs of salivary glands from adult female X. cheopis yielded a total of 7432 coding sequences functionally classified into 25 classes, of which the secreted protein class was the largest. The translated transcripts also served as a reference database for the proteomic study, which identified peptides from 610 different proteins. Both approaches revealed that the acid phosphatase family is the most abundant salivary protein group from X. cheopis. Additionally, we report here novel sequences similar to the FS-H family, apyrases, odorant and hormone-binding proteins, antigen 5-like proteins, adenosine deaminases, peptidase inhibitors from different subfamilies, proteins rich in Glu, Gly, and Pro residues, and several potential secreted proteins with unknown function. SIGNIFICANCE: The rat flea X. cheopis is the main vector of Yersinia pestis, the etiological agent of the bubonic plague responsible for three major pandemics that marked human history and remains a burden to human health. In addition to Y. pestis fleas can also transmit other medically relevant pathogens including Rickettsia spp. and Bartonella spp. The studies of salivary proteins from other hematophagous vectors highlighted the importance of such molecules for blood acquisition and pathogen transmission. However, despite the historical and clinical importance of X. cheopis little is known regarding their salivary gland contents and potential activities. Here we provide a comprehensive analysis of X. cheopis salivary composition using next generation sequencing methods paired with LC-MS/MS analysis, revealing its unique composition compared to the sialomes of other blood-feeding arthropods, and highlighting the different pathways taken during the evolution of salivary gland concoctions. In the absence of the X. cheopis genome sequence, this work serves as an extended reference for the identification of potential pharmacological proteins and peptides present in flea saliva.

Project description:BackgroundThe cat flea, Ctenocephalides felis, is prevalent worldwide, will parasitize animal reservoirs of plague, and is associated with human habitations in known plague foci. Despite its pervasiveness, limited information is available about the cat flea's competence as a vector for Yersinia pestis. It is generally considered to be a poor vector, based on studies examining early-phase transmission during the first week after infection, but transmission potential by the biofilm-dependent proventricular-blocking mechanism has never been systematically evaluated. In this study, we assessed the vector competence of cat fleas by both mechanisms. Because the feeding behavior of cat fleas differs markedly from important rat flea vectors, we also examined the influence of feeding behavior on transmission dynamics.Methodology/principal findingsGroups of cat fleas were infected with Y. pestis and subsequently provided access to sterile blood meals twice-weekly, 5 times per week, or daily for 4 weeks and monitored for infection, the development of proventricular biofilm and blockage, mortality, and the ability to transmit. In cat fleas allowed prolonged, daily access to blood meals, mimicking their natural feeding behavior, Y. pestis did not efficiently colonize the digestive tract and could only be transmitted during the first week after infection. In contrast, cat fleas that were fed intermittently, mimicking the feeding behavior of the efficient vector Xenopsylla cheopis, could become blocked and regularly transmitted Y. pestis for 3-4 weeks by the biofilm-mediated mechanism, but early-phase transmission was not detected.ConclusionsThe normal feeding behavior of C. felis, more than an intrinsic resistance to infection or blockage by Y. pestis, limits its vector competence. Rapid turnover of midgut contents results in bacterial clearance and disruption of biofilm accumulation in the proventriculus. Anatomical features of the cat flea foregut may also restrict transmission by both early-phase and proventricular biofilm-dependent mechanisms.

Dataset Information

Evaluation of the murine immune response to Xenopsylla cheopis flea saliva and its effect on transmission of Yersinia pestis.

Background/aims

Methods/principal findings

Conclusions

Publications

Evaluation of the murine immune response to Xenopsylla cheopis flea saliva and its effect on transmission of Yersinia pestis.

Similar Datasets

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