Schiavoni Ilaria, Fedele Giorgio, Quattrini Adriano, Bianco Manuela, Schnoeller Corinna, Openshaw Peter J, Locht Camille, Ausiello Clara M
Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy.
Centre for Respiratory Infection, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
PLoS One. 2014 Jun 26;9(6):e100166. doi: 10.1371/journal.pone.0100166. eCollection 2014.
Respiratory Syncytial virus (RSV) is the leading cause of acute lower respiratory tract viral infection in young children and a major cause of winter hospitalization. Bordetella pertussis is a common cause of bacterial lung disease, affecting a similar age group. Although vaccines are available for B. pertussis infection, disease rates have recently increased in many countries. We have therefore developed a novel live attenuated B. pertussis strain (BPZE1), which has recently undergone a successful clinical phase I trial. In mice, BPZE1 provides protection against disease caused by respiratory viral challenge. Here, we analyze the effect of BPZE1 on antiviral T cell responses induced by human monocyte-derived dendritic cells (MDDC). We found that BPZE1 influences antiviral immune responses at several levels, enhancing MDDC maturation, IL-12p70 production, and shifting T cell cytokine profile towards a Th1/Th17 pattern. These data were supported by the intracellular signaling analysis. RSV infection of MDDC caused MyD88-independent STAT1 phosphorylation, whereas BPZE1 activated MyD88-dependent signaling pathways; co-infection caused both pathways to be activated. These findings suggest that BPZE1 given during infancy might improve the course and outcome of viral lung disease in addition to providing specific protection against B. pertussis infection.
呼吸道合胞病毒（RSV）是幼儿急性下呼吸道病毒感染的主要病因，也是冬季住院的主要原因。百日咳博德特氏菌是细菌性肺部疾病的常见病因，影响相似年龄组人群。尽管有针对百日咳博德特氏菌感染的疫苗，但最近许多国家的发病率有所上升。因此，我们研发了一种新型减毒活百日咳博德特氏菌菌株（BPZE1），该菌株最近已成功完成I期临床试验。在小鼠中，BPZE1可提供针对呼吸道病毒攻击所致疾病的保护作用。在此，我们分析了BPZE1对人单核细胞衍生树突状细胞（MDDC）诱导的抗病毒T细胞反应的影响。我们发现BPZE1在多个层面影响抗病毒免疫反应，增强MDDC成熟、IL-12p70产生，并使T细胞细胞因子谱向Th1/Th17模式转变。细胞内信号分析支持了这些数据。MDDC感染RSV导致MyD88非依赖性STAT1磷酸化，而BPZE1激活MyD88依赖性信号通路；共感染导致两条通路均被激活。这些发现表明，婴儿期给予BPZE1除了能提供针对百日咳博德特氏菌感染的特异性保护外，还可能改善病毒性肺部疾病的病程和预后。
