tetano
Editor, Senior Moderator
Cell Rep
. 2025 Sep 16;44(10):116312.
doi: 10.1016/j.celrep.2025.116312. Online ahead of print. Innate immune molecular landscape following controlled human influenza virus infection
William Thistlethwaite[SUP] 1 [/SUP], Sindhu Vangeti[SUP] 2 [/SUP], Wan-Sze Cheng[SUP] 3 [/SUP], Pankaj Agarwal[SUP] 4 [/SUP], Antonio Cappuccio[SUP] 3 [/SUP], Wenliang Wang[SUP] 5 [/SUP], Bei Wei[SUP] 6 [/SUP], Rachel Myers[SUP] 4 [/SUP], Aliza B Rubenstein[SUP] 3 [/SUP], Daniel Chawla[SUP] 7 [/SUP], Manoj Hariharan[SUP] 5 [/SUP], Micah T McClain[SUP] 4 [/SUP], Thomas W Burke[SUP] 4 [/SUP], Steven H Kleinstein[SUP] 8 [/SUP], Joseph R Ecker[SUP] 9 [/SUP], Christopher W Woods[SUP] 4 [/SUP], William J Greenleaf[SUP] 6 [/SUP], Xi Chen[SUP] 10 [/SUP], Irene Ramos[SUP] 11 [/SUP], Elena Zaslavsky[SUP] 3 [/SUP], Thomas G Evans[SUP] 12 [/SUP], Olga G Troyanskaya[SUP] 13 [/SUP], Stuart C Sealfon[SUP] 14 [/SUP]
Affiliations
Viral infections can induce prolonged changes in innate immunity. Here, we use blood samples from a human influenza H3N2 challenge study (NCT03883113) to perform comprehensive multi-omics analyses. We detect remodeling of immune programs in circulating innate immune cells that persist after resolution of the infection. We find changes associated with suppressed inflammation, including decreased cytokine and AP-1 gene expression as well as decreased accessibility at AP-1 targets and interleukin-related gene promoter regions. We also find decreased histone deacetylase gene expression, increased MAP kinase gene expression, and increased accessibility at interferon-related gene promoter regions. Genes involved in inflammation and methylation remodeling show modulation of gene-chromatin site regulatory circuit activity. These results reveal a coordinated rewiring of the molecular landscape in innate immune cells induced by mild influenza virus infection.
Keywords: CP: Immunology; CP: Molecular biology; human challenge; influenza; innate immunity; multi-omics; scATAC-seq; scRNA-seq; transcriptomics.
. 2025 Sep 16;44(10):116312.
doi: 10.1016/j.celrep.2025.116312. Online ahead of print. Innate immune molecular landscape following controlled human influenza virus infection
William Thistlethwaite[SUP] 1 [/SUP], Sindhu Vangeti[SUP] 2 [/SUP], Wan-Sze Cheng[SUP] 3 [/SUP], Pankaj Agarwal[SUP] 4 [/SUP], Antonio Cappuccio[SUP] 3 [/SUP], Wenliang Wang[SUP] 5 [/SUP], Bei Wei[SUP] 6 [/SUP], Rachel Myers[SUP] 4 [/SUP], Aliza B Rubenstein[SUP] 3 [/SUP], Daniel Chawla[SUP] 7 [/SUP], Manoj Hariharan[SUP] 5 [/SUP], Micah T McClain[SUP] 4 [/SUP], Thomas W Burke[SUP] 4 [/SUP], Steven H Kleinstein[SUP] 8 [/SUP], Joseph R Ecker[SUP] 9 [/SUP], Christopher W Woods[SUP] 4 [/SUP], William J Greenleaf[SUP] 6 [/SUP], Xi Chen[SUP] 10 [/SUP], Irene Ramos[SUP] 11 [/SUP], Elena Zaslavsky[SUP] 3 [/SUP], Thomas G Evans[SUP] 12 [/SUP], Olga G Troyanskaya[SUP] 13 [/SUP], Stuart C Sealfon[SUP] 14 [/SUP]
Affiliations
- PMID: 40966076
- DOI: 10.1016/j.celrep.2025.116312
Viral infections can induce prolonged changes in innate immunity. Here, we use blood samples from a human influenza H3N2 challenge study (NCT03883113) to perform comprehensive multi-omics analyses. We detect remodeling of immune programs in circulating innate immune cells that persist after resolution of the infection. We find changes associated with suppressed inflammation, including decreased cytokine and AP-1 gene expression as well as decreased accessibility at AP-1 targets and interleukin-related gene promoter regions. We also find decreased histone deacetylase gene expression, increased MAP kinase gene expression, and increased accessibility at interferon-related gene promoter regions. Genes involved in inflammation and methylation remodeling show modulation of gene-chromatin site regulatory circuit activity. These results reveal a coordinated rewiring of the molecular landscape in innate immune cells induced by mild influenza virus infection.
Keywords: CP: Immunology; CP: Molecular biology; human challenge; influenza; innate immunity; multi-omics; scATAC-seq; scRNA-seq; transcriptomics.