The role of the spleen in fighting malaria

06 June 2013

 

Diagram showing splenic myelopoiesis

Diagram showing splenic myelopoiesis (Click to view larger image)

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-γ induced chemokines, byNikolai Belyaev, Judit Biró, Jean Langhorne and Alexandre Potocnik, is published in PLOS Pathogens.

  • Increased production in the spleen of myeloid cells, which are the precursors to some types of blood cell and are usually produced in the bone marrow, helps to combat malaria. 
  • The findings, from the MRC's National Institute for Medical Research, are hoped to eventually lead to new cell-based methods to fight the disease. 
  • Malaria remains one of the most devastating diseases in the developing world - one report showed it caused 1.2 million deaths in 2010 alone. In Africa, a child dies every minute from malaria. The most commonly used drugs are failing rapidly due to resistance, alternatives are expensive and there is no vaccine.