TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment
Toll-like receptor 7 (TLR7) is an endosomal Pathogen-Associated Molecular Pattern (PAMP) receptor that senses single-stranded RNA (ssRNA) and whose engagement results in the production of type I IFN and pro-inflammatory cytokines upon viral exposure. Recent genetic studies have established that a dy...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2023-04-01
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| Series: | Journal of Innate Immunity |
| Online Access: | https://www.karger.com/Article/FullText/530249 |
| _version_ | 1797828680467087360 |
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| author | Miriam Simón-Fuentes Cristina Herrero Lucia Acero-Riaguas Concha Nieto Fatima Lasala Nuria Labiod Joanna Luczkowiak Bárbara Alonso Rafael Delgado Maria Colmenares Ángel L. Corbí Ángeles Domínguez-Soto |
| author_facet | Miriam Simón-Fuentes Cristina Herrero Lucia Acero-Riaguas Concha Nieto Fatima Lasala Nuria Labiod Joanna Luczkowiak Bárbara Alonso Rafael Delgado Maria Colmenares Ángel L. Corbí Ángeles Domínguez-Soto |
| author_sort | Miriam Simón-Fuentes |
| collection | DOAJ |
| description | Toll-like receptor 7 (TLR7) is an endosomal Pathogen-Associated Molecular Pattern (PAMP) receptor that senses single-stranded RNA (ssRNA) and whose engagement results in the production of type I IFN and pro-inflammatory cytokines upon viral exposure. Recent genetic studies have established that a dysfunctional TLR7-initiated signaling is directly linked to the development of inflammatory responses. We present evidences that TLR7 is preferentially expressed by monocyte-derived macrophages generated in the presence of M-CSF (M-MØ). We now show that TLR7 activation in M-MØ triggers a weak MAPK, NFκB and STAT1 activation and results in low production of type I IFN. Of note, TLR7 engagement re-programs MAFB+ M-MØ towards a pro-inflammatory transcriptional profile characterized by the expression of neutrophil-attracting chemokines (CXCL1-3, CXCL5, CXCL8), whose expression is dependent on the transcription factors MAFB and AhR. Moreover, TLR7-activated M-MØ display enhanced pro-inflammatory responses and a stronger production of neutrophil-attracting chemokines upon secondary stimulation. As aberrant TLR7 signaling and enhanced pulmonary neutrophil/lymphocyte ratio associate with impaired resolution of virus-induced inflammatory responses, these results suggest that targeting macrophage TLR7 might be a therapeutic strategy for viral infections where monocyte-derived macrophages exhibit a pathogenic role. |
| first_indexed | 2024-04-09T13:08:14Z |
| format | Article |
| id | doaj.art-a5647017ecc84648a4b20c33f09bd511 |
| institution | Directory Open Access Journal |
| issn | 1662-811X 1662-8128 |
| language | English |
| last_indexed | 2024-04-09T13:08:14Z |
| publishDate | 2023-04-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Journal of Innate Immunity |
| spelling | doaj.art-a5647017ecc84648a4b20c33f09bd5112023-05-12T12:24:17ZengKarger PublishersJournal of Innate Immunity1662-811X1662-81282023-04-011110.1159/000530249530249TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitmentMiriam Simón-Fuenteshttps://orcid.org/0000-0002-8503-0174Cristina HerreroLucia Acero-RiaguasConcha Nietohttps://orcid.org/0000-0003-0790-3440Fatima Lasalahttps://orcid.org/0000-0001-8183-1866Nuria LabiodJoanna Luczkowiakhttps://orcid.org/0000-0001-6950-9372Bárbara AlonsoRafael DelgadoMaria Colmenareshttps://orcid.org/0000-0003-4114-277XÁngel L. Corbíhttps://orcid.org/0000-0003-1980-5733Ángeles Domínguez-SotoToll-like receptor 7 (TLR7) is an endosomal Pathogen-Associated Molecular Pattern (PAMP) receptor that senses single-stranded RNA (ssRNA) and whose engagement results in the production of type I IFN and pro-inflammatory cytokines upon viral exposure. Recent genetic studies have established that a dysfunctional TLR7-initiated signaling is directly linked to the development of inflammatory responses. We present evidences that TLR7 is preferentially expressed by monocyte-derived macrophages generated in the presence of M-CSF (M-MØ). We now show that TLR7 activation in M-MØ triggers a weak MAPK, NFκB and STAT1 activation and results in low production of type I IFN. Of note, TLR7 engagement re-programs MAFB+ M-MØ towards a pro-inflammatory transcriptional profile characterized by the expression of neutrophil-attracting chemokines (CXCL1-3, CXCL5, CXCL8), whose expression is dependent on the transcription factors MAFB and AhR. Moreover, TLR7-activated M-MØ display enhanced pro-inflammatory responses and a stronger production of neutrophil-attracting chemokines upon secondary stimulation. As aberrant TLR7 signaling and enhanced pulmonary neutrophil/lymphocyte ratio associate with impaired resolution of virus-induced inflammatory responses, these results suggest that targeting macrophage TLR7 might be a therapeutic strategy for viral infections where monocyte-derived macrophages exhibit a pathogenic role.https://www.karger.com/Article/FullText/530249 |
| spellingShingle | Miriam Simón-Fuentes Cristina Herrero Lucia Acero-Riaguas Concha Nieto Fatima Lasala Nuria Labiod Joanna Luczkowiak Bárbara Alonso Rafael Delgado Maria Colmenares Ángel L. Corbí Ángeles Domínguez-Soto TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment Journal of Innate Immunity |
| title | TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment |
| title_full | TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment |
| title_fullStr | TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment |
| title_full_unstemmed | TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment |
| title_short | TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment |
| title_sort | tlr7 activation in m csf dependent monocyte derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment |
| url | https://www.karger.com/Article/FullText/530249 |
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