Abstract Hematopoietic stem and progenitor cells (HSPC) 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 HSPC 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 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 HSPC 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.
Fenner et al. (Thu,) studied this question.