“Emergency” granulopoiesis in G-CSF–deficient mice in response to Candida albicans infection

Abstract

Abstract Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein believed to play an important role in regulating granulopoiesis both at steady state and during an “emergency” situation. Generation of G-CSF and G-CSF receptor–deficient mice by gene targeting has demonstrated unequivocally the importance of G-CSF in the regulation of baseline granulopoiesis. This study attempted to define the physiologic role of G-CSF during an emergency situation by challenging a cohort of wild-type and G-CSF–deficient mice with Candida albicans. Interestingly, after infection, G-CSF–deficient mice developed an absolute neutrophilia that was observed both in blood and bone marrow. In addition, 3 days after Candida infection increased numbers of granulocyte-macrophage (GM) and macrophage (M) progenitors were observed in the bone marrow of G-CSF–deficient mice. Of the cytokines surveyed, interleukin (IL)-6 levels in serum were elevated; interestingly, levels of IL-6 were higher and more sustained in G-CSF–deficient mice infected with C albicans than similarly infected wild-type mice. Despite the higher levels of serum IL-6, this cytokine is dispensable for the observed neutrophilia because candida-infected IL-6–deficient mice, or mice simultaneously deficient in G-CSF and IL-6, developed neutrophilia. Similarly, mice lacking both G-CSF and GM-CSF developed absolute neutrophilia and had elevated numbers of GM and M progenitors in the bone marrow; thus, G-CSF and GM-CSF are dispensable for promoting the emergency response to candidal infection.