Haemopoiesis in mice genetically lacking granulocyte-macrophage colony stimulating factor during chronic infection with Mycobacterium avium

In order to test the role of granulocyte-macrophage colony stimulating fact or (GM-CSF) in haemopoiesis during chronic infection, mice with a targeted disruption of the gene fur GM-CSF were infected intraperitoneally with the facultative intracellular pathogen, Mycobacterium avium. The bacteria sprea d to lungs, liver and spleen and persisted for more than 10 weeks at levels between 10(5) and 10(6) CFU. Bacterial numbers did not differ significantl y between infected GM-CSF-/- and wild-type mice, making this an excellent m odel in which to study the effects of GM-CSF deficiency on haemopoietic cel ls without complications of interpretation relating to differences in bacte rial load. Haemopoietic colony forming cells (CFC) in the bone marrow of GM -CSF-/- mice before infection were not different from wild-type. However, w hereas CFC in wild-type mice increased 1.5-fold with infection, GM-CSF-/- m ice were unable to increase their CFC and numbers were significantly lower than in infected wild-type mice. Cells attracted to the peritoneal cavity o f the GM-CSF-/- mice Following i.p, injection of bacteria were notably lack ing in the large, granular macrophages of activated appearance, which were a feature in wild-type mice. Nitric oxide production by peritoneal cells fr om GM-CSF-/- mice was deficient. Thus, GM-CSF is not critical for haemopoie sis during chronic infection, but in its absence the mice are unable to inc rease their output of haemopoietic cells and there are deficiencies in macr ophage activation.