Bosio Christopher F, Viall Austin K, Jarrett Clayton O, Gardner Donald, Rood Michael P, Hinnebusch B Joseph
Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
Veterinary Pathology Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
PLoS Negl Trop Dis. 2014 Sep 25;8(9):e3196. doi: 10.1371/journal.pntd.0003196. eCollection 2014 Sep.
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.
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.
背景/目的：节肢动物传播的病原体被传播到一个独特的真皮内微环境中，该微环境包括其媒介的唾液。唾液中的免疫调节因子可增强感染性；然而，在某些情况下，对先前未感染叮咬的唾液产生的免疫反应可抑制感染性。大多数鼠疫耶尔森菌的啮齿动物宿主经常遭受跳蚤叮咬，但这对跳蚤传播鼠疫的动态影响从未被研究过。我们研究了小鼠对印鼠客蚤叮咬的先天免疫和获得性免疫反应，以及其对初次接触跳蚤叮咬的小鼠和长期暴露于跳蚤叮咬的小鼠中鼠疫耶尔森菌传播和疾病进展的影响。
方法/主要发现：通过流式细胞术、组织学和抗体检测方法对C57BL/6小鼠对未感染跳蚤叮咬的免疫反应进行了表征。在初次接触跳蚤叮咬的小鼠中，跳蚤叮咬诱导了轻度炎症，中性粒细胞和巨噬细胞向叮咬部位的募集有限。初次接触跳蚤叮咬后立即进行皮内注射鼠疫耶尔森菌的小鼠的感染性和宿主反应与未事先经跳蚤叮咬而感染鼠疫耶尔森菌的小鼠无异。随着暴露时间延长，在实验室小鼠和自然暴露于印鼠客蚤的野生大鼠中均出现了主要针对跳蚤唾液主要成分（一组36 - 45 kDa磷酸酶样蛋白）的IgG1抗体反应，但从未出现过敏反应。在初次接触跳蚤叮咬的小鼠和通过在10周内反复暴露于跳蚤叮咬而对跳蚤唾液致敏的小鼠中，经感染性阻塞跳蚤攻击后最终鼠疫的发病率和进展情况相当。
与许多其他吸血节肢动物不同，小鼠对印鼠客蚤唾液的免疫反应轻微，持续暴露于跳蚤叮咬导致更多的是耐受性而非过敏反应。对跳蚤唾液的免疫反应对小鼠中鼠疫耶尔森菌的传播或鼠疫发病机制没有可检测到的影响。
