Related Experiment Video
Updated: Jul 28, 2026
Isolation of Human Monocytes by Double Gradient Centrifugation and Their Differentiation to Macrophages in Teflon-coated Cell Culture Bags
Published on: September 9, 2014
TLR7 Activation in M-CSF-Dependent Monocyte-Derived Human Macrophages Potentiates Inflammatory Responses and Prompts
Miriam Simón-Fuentes1, Cristina Herrero1, Lucia Acero-Riaguas1
1Myeloid Cell Laboratory, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
Abstract:
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 evidence 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 reprograms 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.
Insights
Toll-like receptor 7 (TLR7) on macrophages drives pro-inflammatory responses and neutrophil chemokine production, suggesting TLR7 as a therapeutic target for viral infections with pathogenic macrophage roles.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Toll-like receptor 7 (TLR7) recognizes single-stranded RNA (ssRNA) and initiates inflammatory responses.
- Dysfunctional TLR7 signaling is linked to inflammatory diseases.
- TLR7 is expressed by M-CSF-generated monocyte-derived macrophages (M-MØ).
Purpose of the Study:
- To investigate TLR7 activation in M-MØ.
- To determine the functional consequences of TLR7 engagement in M-MØ.
- To explore the therapeutic potential of targeting TLR7 in viral infections.
Main Methods:
- M-MØ generation using M-CSF.
- TLR7 activation and subsequent signaling pathway analysis (MAPK, NFκB, STAT1).
- Analysis of type I IFN and chemokine production (CXCL1-3, CXCL5, CXCL8).
- Assessment of transcriptional profiles and transcription factor dependency (MAFB, AhR).
- Evaluation of M-MØ responses upon secondary stimulation.
Main Results:
- TLR7 activation in M-MØ induced weak MAPK, NFκB, and STAT1 activation, with low type I IFN production.
- TLR7 engagement reprogrammed MAFB+ M-MØ towards a pro-inflammatory profile, upregulating neutrophil-attracting chemokines dependent on MAFB and AhR.
- TLR7-activated M-MØ showed enhanced pro-inflammatory responses and increased chemokine production upon secondary stimulation.
Conclusions:
- TLR7 signaling in M-MØ promotes pro-inflammatory responses and neutrophil recruitment.
- Aberrant TLR7 signaling and macrophage activation correlate with impaired viral response resolution.
- Targeting macrophage TLR7 may offer a therapeutic strategy for specific viral infections.
Related Concept Videos
01:15Differentiation of Common Myeloid Progenitor Cells
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...