TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Innate Immunity, Pp 1-1 (2023)
Druh dokumentu: article
ISSN: 1662-811X
1662-8128
DOI: 10.1159/000530249
Popis: 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.
Databáze: Directory of Open Access Journals
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