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Pneumolysin suppresses the initial macrophage pro-inflammatory response to Streptococcus pneumoniae.
Periselneris, Jimstan; Turner, Carolin T; Ercoli, Giuseppe; Szylar, Gabriella; Weight, Caroline M; Thurston, Teresa; Whelan, Matthew; Tomlinson, Gillian; Noursadeghi, Mahdad; Brown, Jeremy.
Afiliación
  • Periselneris J; Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, London, UK.
  • Turner CT; Division of Infection and Immunity, University College London, London, UK.
  • Ercoli G; Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, London, UK.
  • Szylar G; Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, London, UK.
  • Weight CM; Division of Infection and Immunity, University College London, London, UK.
  • Thurston T; MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
  • Whelan M; Division of Infection and Immunity, University College London, London, UK.
  • Tomlinson G; Division of Infection and Immunity, University College London, London, UK.
  • Noursadeghi M; Division of Infection and Immunity, University College London, London, UK.
  • Brown J; Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, London, UK.
Immunology ; 167(3): 413-427, 2022 11.
Article en En | MEDLINE | ID: mdl-35835695
Published data for the Streptococcus pneumoniae virulence factor Pneumolysin (Ply) show contradictory effects on the host inflammatory response to infection. Ply has been shown to activate the inflammasome, but also can bind to MRC-1 resulting in suppression of dendritic cell inflammatory responses. We have used an in vitro infection model of human monocyte-derived macrophages (MDM), and a mouse model of pneumonia to clarify whether pro- or anti-inflammatory effects dominate the effects of Ply on the initial macrophage inflammatory response to S. pneumoniae, and the consequences during early lung infection. We found that infection with S. pneumoniae expressing Ply suppressed tumour necrosis factor (TNF) and interleukin-6 production by MDMs compared to cells infected with ply-deficient S. pneumoniae. This effect was independent of bacterial effects on cell death. Transcriptional analysis demonstrated S. pneumoniae expressing Ply caused a qualitatively similar but quantitatively lower MDM transcriptional response to S. pneumoniae compared to ply-deficient S. pneumoniae, with reduced expression of TNF and type I IFN inducible genes. Reduction of the MDM inflammatory response was prevented by inhibition of SOCS1. In the early lung infection mouse model, the TNF response to ply-deficient S. pneumoniae was enhanced and bacterial clearance increased compared to infection with wild-type S. pneumoniae. Overall, these data show Ply inhibits the initial macrophage inflammatory response to S. pneumoniae, probably mediated through SOCS1, and this was associated with improved immune evasion during early lung infection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Streptococcus pneumoniae / Inflamasomas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Immunology Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Streptococcus pneumoniae / Inflamasomas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Immunology Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido