title: Evaluation of the murine immune response to Xenopsylla cheopis flea saliva and its effect on transmission of Yersinia pestis.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Bosio
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Austin K
authors.initials: AK
authors.lastname: Viall
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Clayton O
authors.initials: CO
authors.lastname: Jarrett
authors.affiliation: Veterinary Pathology Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Donald
authors.initials: D
authors.lastname: Gardner
authors.affiliation: Los Angeles County Department of Public Health, Baldwin Park, California.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rood
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: B Joseph
authors.initials: BJ
authors.lastname: Hinnebusch
mesh_terms: D000818:Animals; D005260:Female; D006790:Host-Parasite Interactions / Q000276:immunology; D007299:Insect Bites and Stings / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D007303:Insect Vectors / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010930:Plague / Q000276:immunology / Q000382:microbiology / Q000635:transmission*; D012376:Rodent Diseases / Q000276:immunology* / Q000382:microbiology / Q000635:transmission*; D012463:Saliva / Q000276:immunology / Q000382:microbiology*; D058260:Xenopsylla / Q000276:immunology / Q000382:microbiology*; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity*