| 研究実績の概要 |
People who previously infected with malaria do not gain sterile immunity and are still susceptible to re-infection throughout their lives. Studies showed that malaria causes compromised immunity which leads to increased susceptibility to other infections. Previously we found that malaria causes dysregulation of bone remodeling due to accumulation of Plasmodium parasite products within the bone marrow which is the site for hematopoiesis to produce immune cells. We found that malaria infection causes significant changes in bone marrow hematopoiesis. Malaria suppresses hemapoietic stem cell (HSC) quiescence to promote progenitor cell differentiation potential biased to myelopoiesis, while suppressing lymphopoiesis. To understand the mechanism, we examined the HSC niches that provide survival and differentiation signals for hematopoiesis. Using flow cytometry and 3D microscopy imaging, we found that malaria causes vasodilation, inhibits osteoblasts, and reduces CXCL12-abundant reticular (CAR) cells which surround sinusoidal vessels. Cytokines from CAR cells and osteoblasts are important for hematopoiesis and lymphopoiesis. Gene transcriptomic analysis revealed that malaria suppresses lymphopoiesis through the inhibition of cytokines required for lymphopoiesis. Recovery from malaria infection allowed CAR cells and osteoblast to repopulate, however did not reverse the differentiation potential of hematopoietic progenitor cells.
|
