Search

Your search keyword '"Humphreys IR"' showing total 2 results
Start Over Author "Humphreys IR" Journal nature communications
2 results on '"Humphreys IR"'

1. IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses

Author

Clement, M, Forbester, JL, Marsden, M, Sabberwal, P, Sommerville, MS, Wellington, D, Dimonte, S, Clare, S, Harcourt, K, Yin, Z, Nobre, L, Antrobus, R, Jin, B, Chen, M, Makvandi-Nejad, S, Lindborg, JA, Strittmatter, SM, Weekes, MP, Stanton, RJ, Dong, T, Humphreys, IR, Clement, M [0000-0002-9280-5281], Wellington, D [0000-0002-9277-0306], Yin, Z [0000-0002-2044-5838], Strittmatter, SM [0000-0001-8188-3092], Weekes, MP [0000-0003-3196-5545], Stanton, RJ [0000-0002-6799-1182], Humphreys, IR [0000-0002-9512-5337], and Apollo - University of Cambridge Repository

Subjects
Multidisciplinary, Interleukin-6, SARS-CoV-2, Nogo Proteins, 631/250/255/2514, article, COVID-19, Membrane Proteins, RNA-Binding Proteins, General Physics and Astronomy, 631/250/262, 13/106, General Chemistry, 631/250/254, 13, 14, Toll-Like Receptor 2, General Biochemistry, Genetics and Molecular Biology, Mice, 13/21, 13/51, 14/63, Animals, Cytokines, Humans
Abstract

Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that limits viral pathogenesis and exerts poorly understood immunoregulatory functions. Here, using human and mouse models, we demonstrate that IFITM3 promotes MyD88-dependent, TLR-mediated IL-6 production following exposure to cytomegalovirus (CMV). IFITM3 also restricts IL-6 production in response to influenza and SARS-CoV-2. In dendritic cells, IFITM3 binds to the reticulon 4 isoform Nogo-B and promotes its proteasomal degradation. We reveal that Nogo-B mediates TLR-dependent pro-inflammatory cytokine production and promotes viral pathogenesis in vivo, and in the case of TLR2 responses, this process involves alteration of TLR2 cellular localization. Nogo-B deletion abrogates inflammatory cytokine responses and associated disease in virus-infected IFITM3-deficient mice. Thus, we uncover Nogo-B as a driver of viral pathogenesis and highlight an immunoregulatory pathway in which IFITM3 fine-tunes the responsiveness of myeloid cells to viral stimulation.

Published
2022
Full Text
View/download PDF

2. Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases.

Author

Singhania A, Graham CM, Gabryšová L, Moreira-Teixeira L, Stavropoulos E, Pitt JM, Chakravarty P, Warnatsch A, Branchett WJ, Conejero L, Lin JW, Davidson S, Wilson MS, Bancroft G, Langhorne J, Frickel E, Sesay AK, Priestnall SL, Herbert E, Ioannou M, Wang Q, Humphreys IR, Dodd J, Openshaw PJM, Mayer-Barber KD, Jankovic D, Sher A, Lloyd CM, Baldwin N, Chaussabel D, Papayannopoulos V, Wack A, Banchereau JF, Pascual VM, and O'Garra A

Subjects
Animals, Burkholderia pseudomallei, Candida albicans, Candidiasis immunology, Candidiasis microbiology, Gene Expression Regulation immunology, Influenza A Virus, H3N2 Subtype, Interferon Type I blood, Interferon Type I genetics, Interferon-gamma blood, Interferon-gamma genetics, Lung, Melioidosis immunology, Mice, Mice, Inbred C57BL, Orthomyxoviridae Infections genetics, Orthomyxoviridae Infections immunology, Orthomyxoviridae Infections virology, Receptor, Interferon alpha-beta, Receptors, Interferon, Respiratory Syncytial Virus Infections immunology, Interferon gamma Receptor, Candidiasis metabolism, Interferon Type I metabolism, Interferon-gamma metabolism, Melioidosis metabolism, Orthomyxoviridae Infections metabolism, Respiratory Syncytial Virus Infections metabolism
Abstract

Understanding how immune challenges elicit different responses is critical for diagnosing and deciphering immune regulation. Using a modular strategy to interpret the complex transcriptional host response in mouse models of infection and inflammation, we show a breadth of immune responses in the lung. Lung immune signatures are dominated by either IFN-γ and IFN-inducible, IL-17-induced neutrophil- or allergy-associated gene expression. Type I IFN and IFN-γ-inducible, but not IL-17- or allergy-associated signatures, are preserved in the blood. While IL-17-associated genes identified in lung are detected in blood, the allergy signature is only detectable in blood CD4 + effector cells. Type I IFN-inducible genes are abrogated in the absence of IFN-γ signaling and decrease in the absence of IFNAR signaling, both independently contributing to the regulation of granulocyte responses and pathology during Toxoplasma gondii infection. Our framework provides an ideal tool for comparative analyses of transcriptional signatures contributing to protection or pathogenesis in disease.

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results