Hematopoietic remodeling in interferon-gamma-deficient mice infected with mycobacteria.
Control of intracellular bacterial infections requires interferon-gamma (IFN-gamma) both for establishing a Th1 T-cell response and for activating macrophages to kill the bacteria. Exposure of mice deficient in IFN-gamma to mycobacterial infection produces an immune response characterized by a Th2 T-cell phenotype, florid bacterial growth, and death. We report here that IFN-gamma-deficient mice infected with mycobacteria also undergo a dramatic remodeling of the hematopoietic system. Myeloid cell proliferation proceeds unchecked throughout the course of mycobacterial infection, resulting in a transition to extramedullary hematopoiesis. The splenic architecture of infected IFN-gamma-deficient mice is completely effaced by expansion of macrophages, granulocytes, and extramedullary hematopoietic tissue. These features coincide with splenomegaly, an increase in splenic myeloid colony-forming activity, and marked granulocytosis in the peripheral blood. Systemic levels of cytokines are elevated, particularly interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF). These results suggest that in addition to its central role in cellular immunity, IFN-gamma may be a key cytokine in coordinate regulation of immune effector cells and myelopoiesis. This model should be valuable for deciphering the cross-talk between the immune response and hematopoiesis during bacterial infection and for improving our understanding of the mechanisms that control chronic infections.
Murray
P J
PJ
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Young
R A
RA
Daley
G Q
GQ
D000818:Animals; D016207:Cytokines / Q000097:blood / Q000276:immunology; D006410:Hematopoiesis / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology*; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009164:Mycobacterium Infections / Q000097:blood* / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D007371:Interferon-gamma