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The Evolutionary Mechanisms of Hijacking IgM in Plasmodium falciparum

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Malaria remains a significant public health issue worldwide. According to the World Health Organization, around 241 million people contracted malaria globally in 2020, resulting in approximately 627,000 deaths. The disease, a parasitic infection caused by Plasmodium species, is known for its high fatality rate especially in cases caused by the malaria parasite known as Plasmodium falciparum. This parasite infects red blood cells through a process of asexual multiplication, eventually leading to the cells bursting. This, in turn, triggers clinical symptoms such as fever and hemolytic anemia. The importance of antibodies, notably the IgM type, in the body's defense against pathogens, including the P. falciparum, cannot be ignored. As a first line of defense in the body's humoral immune response, IgM antibodies notably neutralize pathogens effectively due to their decavalent binding nature. Investigations into the molecular mechanisms of IgM by research groups such as that of Dr. Junyu Xiao at Peking University's School of Life Sciences have shed more light on its assembly and mucosal transport mechanisms - a vital aspect of its recognition by specific receptors.

Plasmodium falciparum' Innovative Mechanism against IgM

However, in the ongoing 'arms race' between the human host and malaria pathogens, P. falciparum has, over time, developed mechanisms to inhibit the protective role of IgM. It does this by producing proteins such as PfEMP1, which are expressed on the surface of infected cells. These proteins have domains that facilitate binding with several human molecules. Certain members of this protein family, such as VAR2CSA and PfEMP1-TM284VAR1 facilitate the binding of infected cells to chondroitin sulfate on the placental surface or induce the aggregation of red blood cells, respectively - all mechanisms to protect infected cells from the immune system's attack.

A recent study published in Nature Communications titled "Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M" has shed light on the complex molecular mechanisms of P. falciparum proteins binding to IgM. The study purified the extracellular domains of VAR2CSA, TM284VAR1, DBLMSP, and DBLMSP2 and assembled them into complexes with the core region of IgM pentamers. Using cryo-electron microscopy, the study revealed that these parasite proteins interact with IgM in multiple distinct patterns, disrupting its normal function and evading the immune system.

The <em>P. falciparum</em> proteins directly interact with the human pentameric IgM core.Fig 1. The P. falciparum proteins directly interact with the human pentameric IgM core.1

Novel Insights into Plasmodium falciparum' Immune Evasion Tactics

The study found that P. falciparum proteins hijack IgM in three main ways. Firstly, they interfere with the interaction between IgM and its receptor molecules, inhibiting immune signaling pathways. Secondly, they mask known antigenic sites, preventing IgG antibodies from neutralizing the parasite. Finally, they obstruct the activation of the classical complement pathway, hindering IgM's ability to eliminate the parasite.

In conclusion, this work uncovers the complex molecular mechanisms of interaction between P. falciparum -initiating proteins and IgM. Surprisingly, IgM, which should act as an effective weapon of the human immune system against malaria parasites, is 'hijacked' by several parasite molecules and used as a 'shield' to protect the parasite – a fascinating demonstration of the guile of P. falciparum in evading our immune system's defenses.

At Creative Biolabs, we have established a specialized team and advanced technological platform dedicated to non-IgG research. Our experienced researchers not only offer customizable non-IgG antibody development services but also deliver a wide range of IgM antibodies from various species like rats, mice, and Armenian hamsters tailored for different applications. If you require any related service, don't hesitate to contact us for further information or a detailed quotation.


  1. Ji, Chenggong, et al. "Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M." Nature Communications 14.1 (2023): 2650.

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