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Digital cell quantification identifies global immune cell dynamics during influenza infection
Authors:Zeev Altboum  Yael Steuerman  Eyal David  Zohar Barnett‐Itzhaki  Liran Valadarsky  Hadas Keren‐Shaul  Tal Meningher  Ella Mendelson  Michal Mandelboim  Irit Gat‐Viks  Ido Amit
Affiliation:1. Department of Immunology, Weizmann Institute, Rehovot, Israel;2. Cell Research and Immunology Department, Tel Aviv University, Tel Aviv, Israel;3. Central Virology Laboratory, Ministry of Health, Public Health Services, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel;4. Faculty of Life Sciences, Bar‐Ilan University, Ramat Gan, Israel;5. Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel‐Aviv University, Tel‐Aviv, Israel
Abstract:Hundreds of immune cell types work in coordination to maintain tissue homeostasis. Upon infection, dramatic changes occur with the localization, migration, and proliferation of the immune cells to first alert the body of the danger, confine it to limit spreading, and finally extinguish the threat and bring the tissue back to homeostasis. Since current technologies can follow the dynamics of only a limited number of cell types, we have yet to grasp the full complexity of global in vivo cell dynamics in normal developmental processes and disease. Here, we devise a computational method, digital cell quantification (DCQ), which combines genome‐wide gene expression data with an immune cell compendium to infer in vivo changes in the quantities of 213 immune cell subpopulations. DCQ was applied to study global immune cell dynamics in mice lungs at ten time points during 7 days of flu infection. We find dramatic changes in quantities of 70 immune cell types, including various innate, adaptive, and progenitor immune cells. We focus on the previously unreported dynamics of four immune dendritic cell subtypes and suggest a specific role for CD103+ CD11b DCs in early stages of disease and CD8+ pDC in late stages of flu infection.
Keywords:cell quantification  deconvolution approach  dendritic cells  immune cell dynamics  influenza infection
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