Live attenuated B. pertussis BPZE1 rescues the immune functions of Respiratory Syncytial virus infected human dendritic cells by promoting Th1/Th17 responses

• Published in: PloS one 2014-06, Vol.9 (6), p.e100166-e100166
• Main Authors: Schiavoni, Ilaria, Fedele, Giorgio, Quattrini, Adriano, Bianco, Manuela, Schnoeller, Corinna, Openshaw, Peter J, Locht, Camille, Ausiello, Clara M
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Antiviral agents; Bacteria; Bacterial infections; Biology and life sciences; Blood & organ donations; Bordetella pertussis; Bordetella pertussis - immunology; Cell Proliferation; Children; Cytokines; Cytokines - biosynthesis; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - virology; Gene Expression Profiling; Helper cells; Human behavior; Humans; Immune response; Infection; Infections; Inflammation; Influenza; Interleukin 12; Intracellular signalling; Kinases; Lung diseases; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Mice; Monocytes; Monocytes - cytology; MyD88 protein; Pathways; Pertussis; Pertussis Vaccine - immunology; Phenotype; Phosphorylation; Respiratory syncytial virus; Respiratory Syncytial Viruses - physiology; Respiratory tract; Respiratory tract diseases; Signal Transduction; Stat1 protein; T cells; Th1 Cells - cytology; Th1 Cells - immunology; Th17 Cells - cytology; Th17 Cells - immunology; Vaccines; Vaccines, Attenuated - immunology; Viral infections; Viruses; Whooping cough
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0100166

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.