Essential roles for granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF in the sustained hematopoietic response of Listeria monocytogenes-infected mice.
The in vivo roles of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte (G)-CSF were studied in factor-deficient gene-targeted knockout mice infected with the facultative intracellular bacterium Listeria monocytogenes. Previous results showed that G-CSF-/- mice had an underlying selective deficiency in granulopoiesis, but GM-CSF-/- mice had little disturbance in resting hematopoiesis. Nevertheless, in this study it is revealed that 3 days after intraperitoneal infection with 2 x 10(5) Listeria, GM-CSF-/- mice harbored 50-fold more organisms in their spleen and liver than similarly infected wild-type mice. This was accompanied by a severe depletion of bone marrow hematopoietic cells and a deficient inflammatory response in their peritoneal cavity. Thus, GM-CSF is essential for emergency, but not resting, hematopoiesis. In contrast, G-CSF-/- mice were markedly susceptible to low doses (2 x 10(4)) of Listeria intraperitoneally. After infection, the acute (1 day) granulocyte infiltration to the peritoneal cavity was normal compared with wild type, but the more prolonged monocyte response was deficient, reflecting a continued decrease in bone marrow cellularity and hematopoiesis over 3 days, which was not observed in infected wild-type mice. It is thus apparent that G-CSF deficiency affects monocytopoiesis as well as granulopoiesis during infection.
Zhan
Y
Y
Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
Lieschke
G J
GJ
Grail
D
D
Dunn
A R
AR
Cheers
C
C
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D002452:Cell Count; D015169:Colony Count, Microbial; D016179:Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006098:Granulocytes / Q000473:pathology; D006410:Hematopoiesis; D008088:Listeriosis / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000473:pathology; D010529:Peritoneal Cavity / Q000473:pathology; D013154:Spleen / Q000382:microbiology
D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor