National Animal Disease Center, Agricultural Research Service, USDA, Ames, Iowa, USA.
Infect Immun. 2014 Mar;82(3):1092-103. doi: 10.1128/IAI.01115-13. Epub 2013 Dec 23.
Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Most studies addressing virulence factors of B. bronchiseptica utilize isolates derived from hosts other than pigs in conjunction with rodent infection models. Based on previous in vivo mouse studies, we hypothesized that the B. bronchiseptica type III secretion system (T3SS) would be required for maximal disease severity and persistence in the swine lower respiratory tract. To examine the contribution of the T3SS to the pathogenesis of B. bronchiseptica in swine, we compared the abilities of a virulent swine isolate and an isogenic T3SS mutant to colonize, cause disease, and be transmitted from host to host. We found that the T3SS is required for maximal persistence throughout the lower swine respiratory tract and contributed significantly to the development of nasal lesions and pneumonia. However, the T3SS mutant and the wild-type parent are equally capable of transmission among swine by both direct and indirect routes, demonstrating that transmission can occur even with attenuated disease. Our data further suggest that the T3SS skews the adaptive immune response in swine by hindering the development of serum anti-Bordetella antibody levels and inducing an interleukin-10 (IL-10) cell-mediated response, likely contributing to the persistence of B. bronchiseptica in the respiratory tract. Overall, our results demonstrate that the Bordetella T3SS is required for maximal persistence and disease severity in pigs, but not for transmission.
支气管败血波氏杆菌在猪群中普遍存在,在呼吸道疾病中扮演多种角色。大多数研究支气管败血波氏杆菌毒力因子的工作都利用源自猪以外宿主的分离株,并结合啮齿动物感染模型。基于之前的体内小鼠研究,我们假设支气管败血波氏杆菌 III 型分泌系统(T3SS)对于猪下呼吸道中的最大疾病严重程度和持续性是必需的。为了研究 T3SS 对猪支气管败血波氏杆菌发病机制的贡献,我们比较了一种强毒猪分离株和一个同工 T3SS 突变株在定植、引起疾病和在宿主间传播的能力。我们发现 T3SS 对于在下呼吸道中的最大持久性是必需的,并对鼻损伤和肺炎的发展有显著贡献。然而,T3SS 突变株和野生型亲本在通过直接和间接途径在猪之间的传播能力相同,表明即使在疾病减轻的情况下,也可以发生传播。我们的数据进一步表明,T3SS 通过阻碍血清抗博德特氏菌抗体水平的发展和诱导白细胞介素-10(IL-10)细胞介导的反应,来改变猪的适应性免疫反应,这可能有助于支气管败血波氏杆菌在呼吸道中的持续存在。总体而言,我们的结果表明,T3SS 对于猪中的最大持久性和疾病严重程度是必需的,但对于传播不是必需的。