Correlation between natural killer cell activation in the bone marrow and haemopoietic dysfunction following cytomegalovirus infection of mice
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A E Gibbons1, G R Shellam, P Price
1Department of Microbiology, University of Western Australia, Nedlands, Australia.
Abstract:
We describe here the activation of natural killer (NK) cells in the bone marrows and spleens of mice infected with murine cytomegalovirus (MCMV). NK activity at these sites peaked at day 2 to 3 post-infection (p.i.) and declined between days 6 and 10 p.i. in BALB/c and C57BL/6 mice. In BALB/c mice, the increases in NK activity coincided with depletion of colony-forming units of the granulocyte-monocyte lineage (CFU-GM) from the marrow. CFU-GM depletion in MCMV-infected C57BL/6 mice was less severe, despite the presence of activated NK cells in the marrow. Treatment of BALB/c mice with anti-asialo GM1 prior to MCMV infection resulted in less severe CFU-GM depletion at day 2 p.i. than infection with MCMV alone. When homozygous C57BL/6 or CBA/CaH bg/bg mice were infected with MCMV, depletion of marrow CFU-GM was more severe than in their heterozygous littermates. Finally, we observed some inhibition of colony formation when marrow cells from MCMV-infected and uninfected BALB/c donors were mixed and incubated prior to the CFU-GM assay. These results suggest that activated NK cells may contribute to depletion of haemopoietic cells soon after MCMV infection of BALB/c mice, but may limit the loss of these cells in C57BL/6 and CBA/CaH mice.
Insights
Natural killer (NK) cell activation during murine cytomegalovirus (MCMV) infection impacts hematopoietic cells. Activated NK cells may deplete hematopoietic cells in BALB/c mice but protect them in other strains.
Area of Science:
- Immunology
- Virology
- Hematology
Background:
- Murine cytomegalovirus (MCMV) infection triggers immune responses, including natural killer (NK) cell activation.
- Hematopoietic cells in the bone marrow are crucial for blood cell production and can be affected during viral infections.
Purpose of the Study:
- To investigate the role and kinetics of NK cell activation in response to MCMV infection in mice.
- To determine the impact of MCMV-induced NK cell activation on hematopoietic progenitor cells, specifically colony-forming units of the granulocyte-monocyte lineage (CFU-GM).
Main Methods:
- Mice (BALB/c, C57BL/6, CBA/CaH bg/bg) were infected with MCMV.
- NK cell activity was measured in bone marrow and spleen at various time points post-infection.
- CFU-GM levels in the bone marrow were assessed.
- Experiments involved antibody treatment (anti-asialo GM1) and genetic variations (homozygous vs. heterozygous mice).
Main Results:
- NK cell activity peaked at days 2-3 post-infection and declined by days 6-10 in BALB/c and C57BL/6 mice.
- Increased NK activity in BALB/c mice correlated with CFU-GM depletion, which was less severe in C57BL/6 mice.
- Anti-asialo GM1 treatment reduced CFU-GM depletion in BALB/c mice.
- Homozygous mice showed more severe CFU-GM depletion than heterozygous littermates.
- Inhibition of colony formation was observed when mixing marrow cells from infected and uninfected donors.
Conclusions:
- Activated NK cells may contribute to hematopoietic cell depletion early after MCMV infection in BALB/c mice.
- In contrast, NK cells might limit hematopoietic cell loss in C57BL/6 and CBA/CaH mice.
- The effect of NK cells on hematopoiesis during MCMV infection appears to be strain-dependent.