TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung anti-viral immunity.
William David JacksonChiara GiacomassiSophie WardAmber OwenTiago C LuisSarah SpearKevin J WoollardCecilia JohanssonJessica StridMarina BottoPublished in: eLife (2023)
Monocytes are heterogeneous innate effector leukocytes generated in the bone marrow and released into circulation in a CCR2-dependent manner. During infection or inflammation myelopoiesis is modulated to rapidly meet demand for more effector cells. Danger signals from peripheral tissues can influence this process. Herein we demonstrate that repetitive TLR7 stimulation via the epithelial barriers drove a potent emergency bone marrow monocyte response in mice. This process was unique to TLR7 activation and occurred independently of the canonical CCR2 and CX3CR1 axes or prototypical cytokines. The monocytes egressing the bone marrow had an immature Ly6C-high profile and differentiated into vascular Ly6C-low monocytes and tissue macrophages in multiple organs. They displayed a blunted cytokine response to further TLR7 stimulation and reduced lung viral load after RSV and influenza virus infection. These data provide insights into the emergency myelopoiesis likely to occur in response to the encounter of single-stranded RNA viruses at barrier sites.
Keyphrases
- dendritic cells
- bone marrow
- immune response
- toll like receptor
- inflammatory response
- regulatory t cells
- public health
- peripheral blood
- mesenchymal stem cells
- emergency department
- healthcare
- induced apoptosis
- nuclear factor
- sars cov
- oxidative stress
- high frequency
- big data
- gene expression
- cell cycle arrest
- emergency medical
- electronic health record
- cell death
- metabolic syndrome
- signaling pathway
- endoplasmic reticulum stress
- skeletal muscle
- high fat diet induced
- artificial intelligence
- insulin resistance
- respiratory syncytial virus
- cell proliferation
- wild type
- deep learning