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Researchers have shown how increased production of myeloid cells
in the spleen - known as splenic myelopoiesis - helps to combat
malaria.
Dr Alexandre Potocnik and Dr Jean Langhorne at the MRC's
National Institute for Medical Research (NIMR; now part of
the Francis Crick Institute) explained: "Myeloid progenitors
are immature cells that go on to form some types of blood cell.
They play essential roles in the control of infection, such as that
caused by the malaria parasite.
"The spleen, which often becomes enlarged in malaria, is the
main organ that generates the immune response to the malaria
parasite and controls the removal of red blood cells that have been
infected. This process requires increased production of myeloid
cells."
It is well known from experiments that the production and
mobilisation of myeloid cells plays an important role in malaria
and other infections. However, less is known about the more
upstream cell types that produce these myeloid precursor cells,
including haematopoietic (blood) stem cells and progenitor
cells.
To find out more, the scientists studied mice
infected with the malaria parasite Plasmodium
chabaudi.
They discovered a significant reduction in
numbers of cells called bone marrow lineage-negative cells, which
include haematopoietic stem cells and early progenitor cells,
during infection with Plasmodium chabaudi. The scientists
went on to show that the loss of early myeloid progenitors from the
bone marrow was a key feature of malaria infection. Furthermore,
they found that mobilisation of these cells from the bone marrow
resulted in myeloid cell production in the spleen. Crucially, the
increase in myeloid cells in the spleen contributed to the
clearance of parasite-infected red blood
cells.
The authors said: "Our study defined the molecular
signals and interaction of various cell types that lead to the
establishment of splenic myelopoiesis, which actively contributes
to the effective initial control of the parasite by the mouse's
immune system.
"The activated immune system mobilises early myeloid
progenitors out of the bone marrow, thereby transiently
establishing myeloid cell production in the spleen in order to
contain and resolve the infection locally."
They added that further increasing understanding of
these processes may lead to new cell-based methods to treat the
disease.
The paper, Extramedullary myelopoiesis in malaria depends on mobilization of
myeloid-restricted progenitors by IFN-? induced
chemokines, byNikolai Belyaev, Judit Biró,
Jean Langhorne and Alexandre Potocnik, is published in PLOS
Pathogens.