Pathogenic mechanism of severe pneumonia caused by superinfection with influenza virus and oral bacteria

在本研究中，我们发现非致死剂量的流感病毒和几种口腔链球菌（变形链球菌，S。sanguis，S. salivarius、S. equi）使超过60%的小鼠死亡。结果提示，除非致死性流感病毒感染外，经口感染无强毒因子的链球菌也可致死。然而，目前尚不清楚哪种毒力因子是诱导致死性流感-口腔链球菌重叠感染的关键因素，流感HA疫苗免疫小鼠不能保护小鼠免受致死性重叠感染。我们发现流感病毒HA免疫不能完全保护小鼠肺泡上皮细胞免受流感病毒感染，因此，少数流感病毒感染的细胞与口腔细菌共感染。结果表明，需要有效的疫苗佐剂来增强保护性免疫应答，以完全删除流感病毒，以保护免受超级流感病毒的侵害。 ...更多信息 感染在这里，我们测试了两亲性聚（γ-谷氨酸）-接枝-L-苯丙氨酸共聚物（γ-PGA-NP）是否是全身性流感HA疫苗接种的有效佐剂，所述两亲性聚（γ-谷氨酸）-接枝-L-苯丙氨酸共聚物（γ-PGA-NP）来源于某些纳豆芽孢杆菌菌株产生的细菌荚膜外聚合物。用HA疫苗和γ-PGA-NPs的混合物皮下免疫在HA再刺激后诱导更高的单核细胞增殖和γ-干扰素（IFN-γ）、白细胞介素（IL）-4和IL-6的产生，并且不仅增强抗HA中和抗体的产生，而且增强流感病毒特异性细胞介导的免疫应答，包括CTL活性，与单独用HA或HA和铝佐剂的混合物免疫相比。具有γ-PGA-NP的HA疫苗保护小鼠免受致死剂量的同源流感病毒的攻击。结果表明，将γ-PGA-NPs添加到HA疫苗中促进了有效的保护，并鉴定γ-PGA-NPs作为皮下流感病毒疫苗的新的、有效的和强效的候选佐剂。少

In the present study, we found that superinfection with non-lethal doses of influenza virus and several kinds of oral streptococci(Streptococcus mutans, S. sanguis, S. salivarius, S. equi) let more than 60% of mice to death. The result suggests that infection with oral streptocci which do not have severe virulent factor can be lethal in addition to prior non-lethal influenza infection. However, it still remains which virulence foctor is a key mediator for induction of lethal influenza-oral streptococcal superinfection.Immunization of mice with influenza HA vaccine did not protect from the lethal superinfection. We found that influenza HA immunization did not protect from influenza infection with mouse alveolar epithelial cells completely, thus, a few of influenza infected cells were co-infected with oral bacteria. The result indicate that the available vaccine adjuvant that enhances protective immnue responses to delete influenza virus completely is needed for protection from the super … More infection. Here we tested whether amphiphilic poly(γ-glutamic acid)-graft-L-phenylalanine copolymers(γ-PGA-NPs), which are derived from a bacterial capsular exopolymer produced by certain Bacillus natto strains, were an effective adjuvant for systemic influenza HA vaccination. Subcutaneous immunization with a mixture of HA vaccine and γ-PGA-NPs induced higher mononuclear cell proliferation and the production of γ-interferon(IFN-γ), interleukin(IL)-4, and IL-6 upon HA restimulation, and enhanced not only anti-HA neutralizing antibody production but also the influenza virus-specific cell-mediated immune response, including CTL activity, compared with immunization with HA alone or a mixture of HA and aluminum adjuvant. HA vaccine with γ-PGA-NPs protected mice against challenges with lethal doses of homologous influenza virus. The results indicate that adding γ-PGA-NPs to the HA vaccine promotes effective protection, and identify γ-PGA-NPs as a new, effective, and potent candidate adjuvant for a subcutaneous influenza virus vaccine. Less