TLR7 Promotes Emergency Myelopoiesis and Antiviral Immunity

What is it about?

This study explores the impact of repetitive TLR7 stimulation on monocyte response in mice. TLR7 activation at epithelial barriers drives a specific and distinct monopoiesis response that bypasses the requirement of homeostatic cues like CCR2 or CX3CR1. The TLR7-induced monocytes appear to be immature and programmed to differentiate into macrophages, both surveying the endothelial integrity as Ly6C-low monocytes and trans-migrating into different organs to complement tissue resident macrophages. The response is orchestrated by BM-derived myeloid cells capable of transmitting the signals to the BM HSPCs independently from some of the well-known cytokines such as type I and type II IFNs. The study provides insights into the emergency myelopoiesis likely to occur in response to the encounter of single-stranded RNA viruses at barrier sites.

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Why is it important?

This research is important because it sheds light on the mechanisms behind emergency myelopoiesis, a critical host response to injury or infection. It demonstrates that activation of TLR7 at the epithelial barrier of the skin and gut triggers a specific and distinct monopoiesis response, which does not occur after systemic TLR7 activation or activation of other TLRs. Understanding the unique features of this response is essential for developing effective treatments and strategies for viral infections, particularly those caused by single-stranded RNA viruses such as arboviruses and coronaviruses. Key Takeaways: 1. TLR7 activation at epithelial barriers drives a distinct monopoiesis response, increasing blood monocytes that egress from the bone marrow bypassing the requirement of homeostatic cues like CCR2 or CX3CR1. 2. The response is orchestrated by bone marrow-derived myeloid cells capable of transmitting signals to bone marrow hematopoietic stem/progenitor cells independently from known cytokines. 3. This research advances our understanding of TLR7 signalling at epithelial surfaces, which can impact viral responses and contribute to the host response to infections with single-stranded RNA viruses at barrier sites.