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We are analyzing https://www.nature.com/articles/s41467-022-29308-2.

Title:
Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection | Nature Communications
Description:
The pulmonary immune system consists of a network of tissue-resident cells as well as immune cells that are recruited to the lungs during infection and/or inflammation. How these immune components function during an acute poxvirus infection is not well understood. Intranasal infection of mice with vaccinia virus causes lethal pneumonia and systemic dissemination. Here we report that vaccinia C7 is a crucial virulence factor that blocks activation of the transcription factor IRF3. We provide evidence that type II alveolar epithelial cells (AECIIs) respond to pulmonary infection of vaccinia virus by inducing IFN-β and IFN-stimulated genes via the activation of the MDA5 and STING-mediated nucleic acid-sensing pathways and the type I IFN positive feedback loop. This leads to the recruitment and activation of CCR2+ inflammatory monocytes in the infected lungs and subsequent differentiation into Lyve1− interstitial macrophages (Lyve1− IMs), which efficiently engulf viral particles and block viral replication. Our results provide insights into how innate immune sensing of viral infection by lung AECIIs influences the activation and differentiation of CCR2+ inflammatory monocytes to defend against pulmonary poxvirus infection. Smallpox is a highly contagious respiratory pathogen associated with a high mortality rate. Here the authors utilize a mouse model of intranasal vaccinia virus infection and show a C7 gene encoded virulence factor attenuates type I IFN release by lung type II alveolar epithelial cells and reduces lung inflammatory monocyte responses.
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Keywords {🔍}

infection, cells, vacvcl, mice, fig, pubmed, lung, monocytes, vaccinia, article, lungs, virus, cell, google, scholar, vacv, viral, infected, cas, expression, host, day, type, aeciis, intranasal, ifnβ, post, central, gene, aecii, ims, immune, irf, ifn, data, lyve, signaling, ifnb, ifnar, supplementary, results, ccr, epithelial, inflammatory, ccl, macrophages, function, nature, pfu, alveolar,

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nature portfolio rosa26-lox-stop-lox-tdtomato mice privacy policy cd45−cd16/cd32−cd31−epcam+tdtomato+ cd45−cd16/cd32−cd31−epcam+cd104+ scientific advisory board vacv∆c7l-infected ifih1−/−sting1gt/gt mice editing nf-kb-firefly luciferase reporter sars-cov-2 drives development advertising 5 mm isopropyl-β-d-thiogalactopyranoside ifn-β-yellow fluorescent protein sars-cov-2-induced lung immunopathology nf-κb reporter plasmid bacterial expression vector-pet28-sumo cd45−cd31−t1a−sca1−epcam+ research design ifn-β/yfp positive cells sloan-kettering cancer institute basic research author information authors finished pooled libraries tools reprints pure recombinant vacv∆c7l-gfp ifih1−/−sting1gt/gt mice failed ifn-induced genes reveals ifih1−/−sting1gt/gt mice infected nucleic acid-sensing pathways triggers ifn-β production c57bl/6j bone marrow ifih1−/−sting1gt/gt aecii failed viral-specific ifn-γ+cd8+ ifih1−/−sting1gt/gt aecii cells research nature 472 nature 507 nature 517 nature 441 nature 505 nature lineage-negative progenitors mobilize ifn-β production induced control plasmid prl-tk ifnb1-firefly luciferase reporter anti-cd16/cd32 antibody dna-sensing pathways synergize dna-sensing pathway mediated ifn-β/ifnar/stat2 pathway

Schema {🗺️}

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         description:The pulmonary immune system consists of a network of tissue-resident cells as well as immune cells that are recruited to the lungs during infection and/or inflammation. How these immune components function during an acute poxvirus infection is not well understood. Intranasal infection of mice with vaccinia virus causes lethal pneumonia and systemic dissemination. Here we report that vaccinia C7 is a crucial virulence factor that blocks activation of the transcription factor IRF3. We provide evidence that type II alveolar epithelial cells (AECIIs) respond to pulmonary infection of vaccinia virus by inducing IFN-β and IFN-stimulated genes via the activation of the MDA5 and STING-mediated nucleic acid-sensing pathways and the type I IFN positive feedback loop. This leads to the recruitment and activation of CCR2+ inflammatory monocytes in the infected lungs and subsequent differentiation into Lyve1− interstitial macrophages (Lyve1− IMs), which efficiently engulf viral particles and block viral replication. Our results provide insights into how innate immune sensing of viral infection by lung AECIIs influences the activation and differentiation of CCR2+ inflammatory monocytes to defend against pulmonary poxvirus infection. Smallpox is a highly contagious respiratory pathogen associated with a high mortality rate. Here the authors utilize a mouse model of intranasal vaccinia virus infection and show a C7 gene encoded virulence factor attenuates type I IFN release by lung type II alveolar epithelial cells and reduces lung inflammatory monocyte responses.
         datePublished:2022-03-29T00:00:00Z
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      headline:Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection
      description:The pulmonary immune system consists of a network of tissue-resident cells as well as immune cells that are recruited to the lungs during infection and/or inflammation. How these immune components function during an acute poxvirus infection is not well understood. Intranasal infection of mice with vaccinia virus causes lethal pneumonia and systemic dissemination. Here we report that vaccinia C7 is a crucial virulence factor that blocks activation of the transcription factor IRF3. We provide evidence that type II alveolar epithelial cells (AECIIs) respond to pulmonary infection of vaccinia virus by inducing IFN-β and IFN-stimulated genes via the activation of the MDA5 and STING-mediated nucleic acid-sensing pathways and the type I IFN positive feedback loop. This leads to the recruitment and activation of CCR2+ inflammatory monocytes in the infected lungs and subsequent differentiation into Lyve1− interstitial macrophages (Lyve1− IMs), which efficiently engulf viral particles and block viral replication. Our results provide insights into how innate immune sensing of viral infection by lung AECIIs influences the activation and differentiation of CCR2+ inflammatory monocytes to defend against pulmonary poxvirus infection. Smallpox is a highly contagious respiratory pathogen associated with a high mortality rate. Here the authors utilize a mouse model of intranasal vaccinia virus infection and show a C7 gene encoded virulence factor attenuates type I IFN release by lung type II alveolar epithelial cells and reduces lung inflammatory monocyte responses.
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