Synergistic Effects of Influenza and Staphylococcus aureus Toxins on Inflammation Activation and Cytotoxicity in Human Monocytic Cell Lines
In patients with influenza, morbidity and mortality are strongly influenced by infections with Staphylococcus aureus producing high amounts of certain toxins. Here we tested the impact of influenza virus on the pro-inflammatory and cytotoxic actions of a panel of S. aureus virulence factors, includi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-07-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/10/7/286 |
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| author | Marion Jeannoel Jean-Sebastien Casalegno Michèle Ottmann Cédric Badiou Oana Dumitrescu Bruno Lina Gérard Lina |
| author_facet | Marion Jeannoel Jean-Sebastien Casalegno Michèle Ottmann Cédric Badiou Oana Dumitrescu Bruno Lina Gérard Lina |
| author_sort | Marion Jeannoel |
| collection | DOAJ |
| description | In patients with influenza, morbidity and mortality are strongly influenced by infections with Staphylococcus aureus producing high amounts of certain toxins. Here we tested the impact of influenza virus on the pro-inflammatory and cytotoxic actions of a panel of S. aureus virulence factors, including Panton-Valentine Leucocidin (PVL), phenol-soluble modulin α1 (PSMα1) and 3 (PSMα3), α-hemolysin (Hla), and cell wall components, i.e., heat-killed S. aureus (HKSA) and protein A. We initially screened for potential synergic interactions using a standardized in vitro model in influenza-infected continuous human monocytic cell lines. Then we tested the identified associations using an ex vivo model in influenza-infected human monocytes freshly isolated from blood. Co-exposure to influenza virus and HKSA, PVL, PSMα1, and PSMα3 increased NF-κB/AP-1 pathway activation in THP1-XBlue cells, and co-exposure to influenza virus and PVL increased cytotoxicity in U937 cells. In monocytes isolated from blood, the synergy between influenza virus and HKSA was confirmed based on cytokine production (TNF-α, IL-1β, IL-6), and co-exposure to influenza virus and Hla-increased cytotoxicity. Our findings suggest that influenza virus potentiates the pro-inflammatory action of HKSA and contributes to the cytotoxicity of Hla on monocytes. Synergic interactions identified in the cell-line model must be cautiously interpreted since few were relevant in the ex vivo model. |
| first_indexed | 2024-04-14T07:00:18Z |
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| id | doaj.art-85b8cc3742334ed4b3b38d3841dc16c2 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-14T07:00:18Z |
| publishDate | 2018-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-85b8cc3742334ed4b3b38d3841dc16c22022-12-22T02:06:46ZengMDPI AGToxins2072-66512018-07-0110728610.3390/toxins10070286toxins10070286Synergistic Effects of Influenza and Staphylococcus aureus Toxins on Inflammation Activation and Cytotoxicity in Human Monocytic Cell LinesMarion Jeannoel0Jean-Sebastien Casalegno1Michèle Ottmann2Cédric Badiou3Oana Dumitrescu4Bruno Lina5Gérard Lina6Laboratoire de Virologie, Institut des Agents Infectieux, Groupement Hospitalier Nord des Hospices Civils de Lyon, CEDEX 04, 69317 Lyon, FranceLaboratoire de Virologie, Institut des Agents Infectieux, Groupement Hospitalier Nord des Hospices Civils de Lyon, CEDEX 04, 69317 Lyon, FranceLaboratoire de Virologie et Pathologies Humaines Virpath, CIRI, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, CEDEX 08, 69372 Lyon, FrancePathogénie des Staphylocoques, CIRI, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, CEDEX 08, 69372 Lyon, FrancePathogénie des Staphylocoques, CIRI, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, CEDEX 08, 69372 Lyon, FranceLaboratoire de Virologie, Institut des Agents Infectieux, Groupement Hospitalier Nord des Hospices Civils de Lyon, CEDEX 04, 69317 Lyon, FrancePathogénie des Staphylocoques, CIRI, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, CEDEX 08, 69372 Lyon, FranceIn patients with influenza, morbidity and mortality are strongly influenced by infections with Staphylococcus aureus producing high amounts of certain toxins. Here we tested the impact of influenza virus on the pro-inflammatory and cytotoxic actions of a panel of S. aureus virulence factors, including Panton-Valentine Leucocidin (PVL), phenol-soluble modulin α1 (PSMα1) and 3 (PSMα3), α-hemolysin (Hla), and cell wall components, i.e., heat-killed S. aureus (HKSA) and protein A. We initially screened for potential synergic interactions using a standardized in vitro model in influenza-infected continuous human monocytic cell lines. Then we tested the identified associations using an ex vivo model in influenza-infected human monocytes freshly isolated from blood. Co-exposure to influenza virus and HKSA, PVL, PSMα1, and PSMα3 increased NF-κB/AP-1 pathway activation in THP1-XBlue cells, and co-exposure to influenza virus and PVL increased cytotoxicity in U937 cells. In monocytes isolated from blood, the synergy between influenza virus and HKSA was confirmed based on cytokine production (TNF-α, IL-1β, IL-6), and co-exposure to influenza virus and Hla-increased cytotoxicity. Our findings suggest that influenza virus potentiates the pro-inflammatory action of HKSA and contributes to the cytotoxicity of Hla on monocytes. Synergic interactions identified in the cell-line model must be cautiously interpreted since few were relevant in the ex vivo model.http://www.mdpi.com/2072-6651/10/7/286Staphylococcus aureustoxinsinfluenza A virusmonocytecoinfectioninflammationcytotoxicity |
| spellingShingle | Marion Jeannoel Jean-Sebastien Casalegno Michèle Ottmann Cédric Badiou Oana Dumitrescu Bruno Lina Gérard Lina Synergistic Effects of Influenza and Staphylococcus aureus Toxins on Inflammation Activation and Cytotoxicity in Human Monocytic Cell Lines Toxins Staphylococcus aureus toxins influenza A virus monocyte coinfection inflammation cytotoxicity |
| title | Synergistic Effects of Influenza and Staphylococcus aureus Toxins on Inflammation Activation and Cytotoxicity in Human Monocytic Cell Lines |
| title_full | Synergistic Effects of Influenza and Staphylococcus aureus Toxins on Inflammation Activation and Cytotoxicity in Human Monocytic Cell Lines |
| title_fullStr | Synergistic Effects of Influenza and Staphylococcus aureus Toxins on Inflammation Activation and Cytotoxicity in Human Monocytic Cell Lines |
| title_full_unstemmed | Synergistic Effects of Influenza and Staphylococcus aureus Toxins on Inflammation Activation and Cytotoxicity in Human Monocytic Cell Lines |
| title_short | Synergistic Effects of Influenza and Staphylococcus aureus Toxins on Inflammation Activation and Cytotoxicity in Human Monocytic Cell Lines |
| title_sort | synergistic effects of influenza and staphylococcus aureus toxins on inflammation activation and cytotoxicity in human monocytic cell lines |
| topic | Staphylococcus aureus toxins influenza A virus monocyte coinfection inflammation cytotoxicity |
| url | http://www.mdpi.com/2072-6651/10/7/286 |
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