Chacón-Díaz Carlos, Altamirano-Silva Pamela, González-Espinoza Gabriela, Medina María-Concepción, Alfaro-Alarcón Alejandro, Bouza-Mora Laura, Jiménez-Rojas César, Wong Melissa, Barquero-Calvo Elías, Rojas Norman, Guzmán-Verri Caterina, Moreno Edgardo, Chaves-Olarte Esteban
Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.
Infect Immun. 2015 Dec;83(12):4861-70. doi: 10.1128/IAI.00995-15. Epub 2015 Oct 5.
Canine brucellosis caused by Brucella canis is a disease of dogs and a zoonotic risk. B. canis harbors most of the virulence determinants defined for the genus, but its pathogenic strategy remains unclear since it has not been demonstrated that this natural rough bacterium is an intracellular pathogen. Studies of B. canis outbreaks in kennel facilities indicated that infected dogs displaying clinical signs did not present hematological alterations. A virulent B. canis strain isolated from those outbreaks readily replicated in different organs of mice for a protracted period. However, the levels of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-12 in serum were close to background levels. Furthermore, B. canis induced lower levels of gamma interferon, less inflammation of the spleen, and a reduced number of granulomas in the liver in mice than did B. abortus. When the interaction of B. canis with cells was studied ex vivo, two patterns were observed, a predominant scattered cell-associated pattern of nonviable bacteria and an infrequent intracellular replicative pattern of viable bacteria in a perinuclear location. The second pattern, responsible for the increase in intracellular multiplication, was dependent on the type IV secretion system VirB and was seen only if the inoculum used for cell infections was in early exponential phase. Intracellular replicative B. canis followed an intracellular trafficking route undistinguishable from that of B. abortus. Although B. canis induces a lower proinflammatory response and has a stealthier replication cycle, it still displays the pathogenic properties of the genus and the ability to persist in infected organs based on the ability to multiply intracellularly.
由犬布鲁氏菌引起的犬布鲁氏菌病是犬类的一种疾病,且存在人畜共患病风险。犬布鲁氏菌具有该属定义的大多数毒力决定因素,但其致病策略仍不清楚,因为尚未证明这种天然粗糙型细菌是一种细胞内病原体。对犬舍设施中犬布鲁氏菌病暴发的研究表明,出现临床症状的感染犬没有血液学改变。从这些暴发中分离出的一株强毒犬布鲁氏菌菌株能在小鼠的不同器官中长期大量繁殖。然而,血清中肿瘤坏死因子α、白细胞介素-6(IL-6)和IL-12的水平接近背景水平。此外,与流产布鲁氏菌相比,犬布鲁氏菌在小鼠体内诱导产生的γ干扰素水平较低,脾脏炎症较轻,肝脏中的肉芽肿数量减少。当在体外研究犬布鲁氏菌与细胞的相互作用时,观察到两种模式,一种是主要的与非存活细菌相关的分散细胞模式,另一种是在核周位置的存活细菌罕见的细胞内复制模式。第二种模式导致细胞内增殖增加,它依赖于IV型分泌系统VirB,并且只有当用于细胞感染的接种物处于指数早期时才会出现。细胞内复制的犬布鲁氏菌遵循与流产布鲁氏菌无法区分的细胞内运输途径。尽管犬布鲁氏菌诱导的促炎反应较低,并且具有更隐蔽的复制周期,但基于其在细胞内繁殖的能力,它仍然表现出该属的致病特性以及在感染器官中持续存在的能力。