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比较粒细胞无形体病犬模型中犬无形体感染的菌株分析与临床结局。

Comparative strain analysis of Anaplasma phagocytophilum infection and clinical outcomes in a canine model of granulocytic anaplasmosis.

机构信息

Department of Molecular Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

出版信息

Vector Borne Zoonotic Dis. 2011 Mar;11(3):223-9. doi: 10.1089/vbz.2009.0262. Epub 2010 Sep 16.

DOI:10.1089/vbz.2009.0262
PMID:20846015
Abstract

A pilot study was conducted to determine whether existing human or canine strains of Anaplasma phagocytophilum would reproduce clinical disease in experimentally inoculated dogs similar to dogs with naturally acquired granulocytic anaplasmosis. Six hounds were inoculated intravenously with one human and two canine strains of A. phagocytophilum that were propagated in vitro in HL-60 cells or in infected autologous neutrophils. Infected dogs were monitored for lethargy, anorexia, petechiae, lymphadenopathy, and fever. Dogs were assessed for complete blood count (CBC), serum chemistry, and serology (IFA and SNAP® 4Dx®); for A. phagocytophilum blood load by quantitative polymerase chain reaction; and for cytokine production. Prominent clinical signs were generalized lymphadenopathy and scleral injection; only one dog developed fever lasting 4 days. Notable laboratory alterations included sustained leukopenia and thrombocytopenia in all dogs. A. phagocytophilum morulae were noted in blood between days 10 and 11, although all dogs retained A. phagocytophilum DNA in blood through day 60. All dogs seroconverted by days 10-15 by IFA, and by days 17-30 by SNAP 4Dx; cytokine analyses revealed 10-fold increases in interleukin-2 and interleukin-18 in the neutrophil-propagated 98E4 strain-infected dog. All A. phagocytophilum strains produced infection, although canine 98E4 strain reproduced clinical signs, hematologic changes, and inflammatory cytokine elevations most consistent with granulocytic anaplasmosis when recognized clinically. Therefore, this strain should be considered for use in future studies of A. phagocytophilum canine infection models.

摘要

一项初步研究旨在确定现有的人源或犬源嗜吞噬细胞无形体(Anaplasma phagocytophilum)菌株是否会在实验接种的犬中引起类似于自然获得性粒细胞无形体病的临床疾病。将六只猎犬静脉内接种一株人源和两株犬源嗜吞噬细胞无形体,这三种菌株均在 HL-60 细胞或感染的自体嗜中性粒细胞中体外繁殖。对感染的犬进行昏睡、厌食、瘀点、淋巴结病和发热监测。对犬进行全血细胞计数(CBC)、血清化学和血清学(IFA 和 SNAP® 4Dx®)评估;通过定量聚合酶链反应评估嗜吞噬细胞无形体的血液载量;以及细胞因子产生评估。主要临床体征为全身淋巴结病和巩膜注射;只有一只犬出现持续 4 天的发热。显著的实验室改变包括所有犬的白细胞持续减少和血小板减少。在第 10 天至 11 天之间在血液中观察到嗜吞噬细胞无形体菌毛,但所有犬的血液中在第 60 天都保留有嗜吞噬细胞无形体 DNA。所有犬在第 10-15 天通过 IFA、第 17-30 天通过 SNAP 4Dx 检测到血清转化;细胞因子分析显示,在犬源 98E4 株感染犬中,白细胞介素-2 和白细胞介素-18 增加了 10 倍。所有嗜吞噬细胞无形体菌株均产生感染,但当临床上识别时,犬源 98E4 株最能复制临床症状、血液学改变和炎症细胞因子升高,与粒细胞无形体病最为一致。因此,该菌株应考虑用于未来的犬源嗜吞噬细胞无形体感染模型研究。

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