Data from: Aryl hydrocarbon receptor activation alters emergency hematopoiesis during influenza A virus infection
Abstract
Hematopoietic stem and progenitor cells (HSPCs) produce all cells of the blood and immune system in a process known as hematopoiesis. During infection, there is an increased demand for immune cells, which causes HSPCs to rapidly and transiently modify cellular output, a response described as emergency hematopoiesis. Small molecules from the host environment may contribute to signals that regulate emergency hematopoiesis, providing a means to influence important processes during infection. Environmental exposures have long been associated with altered immune responses in the human population and experimental studies. Specifically, chemicals that bind the aryl hydrocarbon receptor (AHR) modulate immune responses in a broad range of contexts, including during viral infection. Separate studies have shown that AHR signaling also influences steady-state hematopoiesis. Using two different AHR ligands, 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and 2-(1H-indol-3-ylcarbonyl)-4-thiazole-carboxylic acid methyl ester (ITE), we characterized the impact of AHR activation on the proportion of HSPC and lineage-committed progenitor cells over the course of an influenza A virus infection in mice. AHR activation via these two ligands had a distinct impact on HSPCs, yet affected monocytes in the blood and lung similarly. For example, AHR activation with TCDD, but not ITE, increased myeloid-biasing among HSPC. However, the frequency of monocytes in the lung was reduced by either TCDD or ITE treatment. Using Vav1CreAhrfxfx mice, we showed that these effects depend on AHR expression in hematopoietic cells. Collectively, these findings highlight the differential effects of AHR ligands and their role in regulating emergency hematopoiesis in response to a common respiratory pathogen.
Dataset DOI: 10.5061/dryad.sf7m0cgkz
Description of the data and file structure
Enclosed are tables of the percentage and number of hematopoietic stem and progenitor cells in the bone marrow of mice, the average percentage and number of platelets, red blood, and monocytes in the blood of mice, and the mean percentage and number of monocytes in the lungs of mice.
Files and variables
File: Data.xlsx
Description: Mean percentage and number of hematopoietic stem and progenitor cells in the bone marrow and cells of the blood in mice
Variables
- Mice were treated with vehicle-control (peanut oil), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or 2-(1H-indol-3-ylcarbonyl)-4-thiazole-carboxylic acid methyl ester (ITE). The following day, mice were infected with the influenza virus (HKx31, 120HAU). Mice were sacrificed on multiple days after infection, and bone marrow, blood, and lungs were collected. Single-cell suspensions of bone marrow and lung were obtained, and cells were stained for flow cytometry. Blood was analyzed bya complete blood count (CBC) analyzer for platelets and red blood cells. Blood was also stained for flow cytometry to identify monocytes. Experiments consisted of 4-9 mice per treatment group per day of infection.
- Data is represented as the mean percentage or number of cells from 4-9 mice per treatment group per day of infection.
- Hematopoietic stem and progenitor cells, monocytes in the blood and lung, are derived from flow cytometry data
- Platelet and red blood cell numbers were derived from a complete blood count (CBC) analyzer.
- Across infection, BM cellularity rises early (peaks ~day 5) and then declines by days 7–12 in both groups, with TCDD generally showing lower or delayed recovery compared to Vehicle. HSPCs expand markedly after infection, peaking around day 7, with TCDD often exaggerating HSPC numbers despite similar or modestly altered percentages. Lineage bias shifts dynamically: early myeloid (MPPGM/MPPM) expansion dominates, while lymphoid (MPPLy) fractions drop at day 5 and rebound strongly by day 7. Overall, TCDD alters the magnitude and timing of hematopoietic responses to infection rather than completely changing lineage trajectories.
Software
Any program that will open a spreadsheet, such as Excel, is recommended.
Supplemental Information
File: Supplemental_Information.docx
Description: Supplementary figures and data tables
Variables
- All data is represented as the mean and standard error
- All statistical testing used in each figure and table is noted in the Figure/Table legend