title: Live attenuated B. pertussis BPZE1 rescues the immune functions of Respiratory Syncytial virus infected human dendritic cells by promoting Th1/Th17 responses.
abstract: 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.
authors: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy.
authors: Ilaria
authors: I
authors: Schiavoni
authors: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy.
authors: Giorgio
authors: G
authors: Fedele
authors: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy.
authors: Adriano
authors: A
authors: Quattrini
authors: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy.
authors: Manuela
authors: M
authors: Bianco
authors: Centre for Respiratory Infection, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Corinna
authors: C
authors: Schnoeller
authors: Centre for Respiratory Infection, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Peter J
authors: PJ
authors: Openshaw
authors: INSERM U1019, Lille, France; Centre National de la Recherche Scientifique UMR8204, Lille, France; Centre d'Infection et Immunité de Lille, Institut Pasteur de Lille, Lille, France; Univ Lille Nord de France, Lille, France.
authors: Camille
authors: C
authors: Locht
authors: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy.
authors: Clara M
authors: CM
authors: Ausiello
mesh_terms: D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000166:cytology; D010567:Pertussis Vaccine / Q000276:immunology*; D010641:Phenotype; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D016207:Cytokines; D010567:Pertussis Vaccine; D014613:Vaccines, Attenuated