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

• Published in: Blood 2000-06, Vol.95 (12), p.3725-3733
• Main Authors: BASU, S, HODGSON, G, ZHANG, H.-H, KATZ, M, QUILICI, C, DUNN, A. R
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Marrow Cells - pathology; Candida albicans; Candidiasis - pathology; Candidiasis - physiopathology; Granulocyte Colony-Stimulating Factor - deficiency; Granulocyte Colony-Stimulating Factor - genetics; Granulocyte Colony-Stimulating Factor - physiology; Granulocyte-Macrophage Colony-Stimulating Factor - deficiency; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - physiology; Granulocytes - cytology; Granulocytes - pathology; Human mycoses; Infectious diseases; Interleukin-6 - deficiency; Interleukin-6 - genetics; Interleukin-6 - physiology; Kidney - cytology; Kidney - pathology; Kinetics; Leukopoiesis - physiology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Miscellaneous mycoses; Mycoses; Receptors, Granulocyte Colony-Stimulating Factor - deficiency; Receptors, Granulocyte Colony-Stimulating Factor - genetics; Receptors, Granulocyte Colony-Stimulating Factor - physiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v95.12.3725

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. (Blood. 2000;95:3725-3733)