Plasmodium spp. parasites are the causative agents of malaria in humans and animals, and they are exceptionally diverse in their morphology and life cycles. They grow and develop in a wide range of host environments, both within blood-feeding mosquitoes, their definitive hosts, and in vertebrates, which are intermediate hosts. This diversity is testament to their exceptional adaptability and poses a major challenge for developing effective strategies to reduce the disease burden and transmission. Following one asexual amplification cycle in the liver, parasites reach high burdens by rounds of asexual replication within red blood cells. A few of these blood-stage parasites make a developmental switch into the sexual stage (or gametocyte), which is essential for transmission. The bone marrow, in particular the haematopoietic niche (in rodents, also the spleen), is a major site of parasite growth and sexual development. This Review focuses on our current understanding of blood-stage parasite development and vascular and tissue sequestration, which is responsible for disease symptoms and complications, and when involving the bone marrow, provides a niche for asexual replication and gametocyte development. Understanding these processes provides an opportunity for novel therapies and interventions.
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The authors thank Chris Moxon (University of Glasgow), Juliane Schär (Humboldt University, Berlin) and members of the Marti laboratory for critical reading of the manuscript and helpful discussions. Research in the Marti laboratory is supported by a Wellcome Senior Investigator award (M.M.), European Research Council Consolidator award BoneMalar (M.M.) and a Wellcome Trust Centre award to the Wellcome Center for Integrative Parasitology. Additional funding comes from a Royal Society Wolfson Merit award (M.M.) and a German Research Foundation postdoctoral fellowship (F.H.).
The authors declare no competing interests.
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Maturation of male and female gametes.
Cell division involving chromosome duplication and genetic exchange.
The only parasite stage that can invade the vertebrate host upon insect bite.
Special capillaries lacking a basal lamina and present in the bone marrow, liver, spleen and adrenal glands.
- Parasitophorous vacuole
A membrane compartment surrounding the parasite and separating it from the host cell.
Or meront. A replicative parasite stage in the vertebrate host producing daughter merozoites.
The only parasite stage that can invade red blood cells.
A non-replicative dormant parasite stage in the vertebrate host liver that can reactivate and lead to relapses.
Immature red blood cells developing in the bone marrow before final maturation in the blood circulation.
A union of male and female gametes where meiosis takes place.
A motile zygote that forms the oocyst upon crossing the basal lamina of the mosquito midgut.
A replicative stage in the mosquito host producing daughter sporozoites.
Equivalent to blood in arthropods and other invertebrates.
- Haematopoietic stem cells
A cell type that gives rise to all blood cells in the process of haematopoiesis.
An extravascular compartment of the bone marrow where haematopoiesis takes place.
Secondary exo-erythrocytic schizonts in avian and reptile malaria parasites.
Defective development of red blood cells, or erythropoiesis.
- Central tolerance
The process of eliminating developing T and B cells that are reactive to the self.
The recurrence of detectable parasitaemia upon clearance to submicroscopic levels.
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Venugopal, K., Hentzschel, F., Valkiūnas, G. et al. Plasmodium asexual growth and sexual development in the haematopoietic niche of the host. Nat Rev Microbiol 18, 177–189 (2020). https://doi.org/10.1038/s41579-019-0306-2