Dynamic Virus-Bacterium Interactions in a Porcine Precision-Cut Lung Slice Coinfection Model: Swine Influenza Virus Paves the Way for Streptococcus suis Infection in a Two-Step Process
Dynamic Virus-Bacterium Interactions in a Porcine Precision-Cut Lung Slice Coinfection Model: Swine Influenza Virus Paves the Way for Streptococcus suis Infection in a Two-Step Process
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DOI：
10.1128/iai.00171-15
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发表时间：
2015-07-01
影响因子：
3.1
通讯作者：
Seitz, M.
中科院分区：
文献类型：
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作者：
Meng, F.;Wu, N. H.;Seitz, M.
猪流感病毒（SIV）和猪链球菌是猪呼吸道的常见病原体，两者都与肺炎有关。这两种病原体的相互作用及其对病原发生的贡献知之甚少。本研究建立了猪精密切割肺切片（PCLS）混合感染模型，分析了SIV初次感染对猪链球菌在不同时间点继发感染的影响。我们发现SIV促进猪链球菌的粘附、定殖和侵袭分两步进行。首先，在初始阶段，这些作用取决于细菌包裹，正如包裹的而不是未包裹的猪链球菌对SIV感染的细胞的选择性粘附所示。其次，在感染后期，SIV通过破坏纤毛上皮细胞促进猪链球菌粘附和侵入更深的组织。这种效应在高毒力SIV亚型H3N2毒株中观察到，但在低毒力亚型H1N1毒株中没有观察到，并且它不依赖于细菌荚膜，因为未包囊化的猪链球菌突变株的行为方式与包囊化的野生型毒株相似。总之，PCLS共感染模型的建立揭示了新的见解SIV和猪链球菌之间的动态相互作用在呼吸道感染。结果表明，至少有两种不同的机制有助于SIV对猪链球菌的有益作用，包括囊膜介导的细菌附着到SIV感染的细胞和涉及病毒介导的纤毛上皮细胞损伤的非囊膜效应。
Swine influenza virus (SIV) and Streptococcus suis are common pathogens of the respiratory tract in pigs, with both being associated with pneumonia. The interactions of both pathogens and their contribution to copathogenesis are only poorly understood. In the present study, we established a porcine precision-cut lung slice (PCLS) coinfection model and analyzed the effects of a primary SIV infection on secondary infection by Streptococcus suis at different time points. We found that SIV promoted adherence, colonization, and invasion of Streptococcus suis in a two-step process. First, in the initial stages, these effects were dependent on bacterial encapsulation, as shown by selective adherence of encapsulated, but not unencapsulated, Streptococcus suis to SIV-infected cells. Second, at a later stage of infection, SIV promoted Streptococcus suis adherence and invasion of deeper tissues by damaging ciliated epithelial cells. This effect was seen with a highly virulent SIV subtype H3N2 strain but not with a low-virulence subtype H1N1 strain, and it was independent of the bacterial capsule, since an unencapsulated Streptococcus suis mutant behaved in a way similar to that of the encapsulated wildtype strain. In conclusion, the PCLS coinfection model established here revealed novel insights into the dynamic interactions between SIV and Streptococcus suis during infection of the respiratory tract. It showed that at least two different mechanisms contribute to the beneficial effects of SIV for Streptococcus suis, including capsule-mediated bacterial attachment to SIV-infected cells and capsule-independent effects involving virus-mediated damage of ciliated epithelial cells.