Plasmodium and its host are based on the game mechanism of RIFIN-LAIR1 co-evolution.
Plasmodium and its host are based on the game mechanism of RIFIN-LAIR1 co-evolution.
In a study published in Cell Reports on August 24, the team of Gao Fu, an academician of the Chinese Academy of Sciences, revealed such a cunning mouse—the molecular mechanism of Plasmodium falciparum immune escape and the host’s countermeasures.
Game: "Crossing the Sea without Covering the Sky" VS "Clues"
Game: "Crossing the Sea without Covering the Sky" VS "Clues" Malaria is a vector-borne disease caused by the plasmodium parasite and transmitted by the bite of female Anopheles mosquitoes
At the end of June this year, the World Health Organization declared China a malaria-free country, which also brought the number of malaria-free countries in the world to 40
"Scientists have discovered that there are six types of malaria parasites that can cause human diseases.
He explained that Plasmodium falciparum can express a variety of proteins such as PfEMP1, STEVOR, and RIFIN after infecting red blood cells.
Where there is fraud, there is anti-fraud
Extracellular segment Ab "LAIR1 is an immunosuppressive receptor expressed on the surface of a variety of immune cells such as NK cells and T cells.
Chinese Academy of Sciences Ab In response to these problems, Gao Fu, Song Hao, Qi Jianxun and others explained the interaction mechanism of Plasmodium falciparum RIFIN protein and host immunosuppressive receptor LAIR1 from the molecular level, and revealed the molecular mechanism of Plasmodium falciparum immune escape and host countermeasures.
"This is the first report on the interaction between RIFIN and LAIR1, which is of great significance to the field
Invasion: "Mingxiu Plank Road" + "Darkness Chencang"
Invasion: "Mingxiu Plank Road" + "Darkness Chencang" How can the malaria parasite suppress the human immune system after it has "hidden the sky"? In the research, the author found that the RIFIN protein not only "built the plank road", but also "didden the warehouse", and combined with the LAIR1 molecule in different ways to inhibit the body's immune mechanism
By analyzing the monomer structure of RIFIN and the structure of the complex between two RIFIN members and LAIR1/LAIR1 Ab , the research team found that the extracellular segment of the RIFIN protein consists of a conserved region and a variable region.
Ab This "watchtower" structure is the "plank road" connecting the RIFIN protein to the LAIR1 molecule
Interestingly, by further comparing the details of the interaction between RIFIN and LAIR1, they found that the binding site of RIFIN and LAIR1 partially overlaps the binding site of LAIR1 and its natural ligand, collagen, indicating that RIFIN may be able to "dark out" by simulating collagen.
In addition, Song Hao said that some studies have found that some RIFIN molecules can bind to another immunosuppressive receptor LILRB1, thereby inhibiting the function of immune cells
.
The comparison found that RIFIN members use different binding sites to bind to LAIR1 or LILRB1.
This phenomenon further indicates the diversity of RIFIN family members
.
Overcome the enemy: enhance "affinity" and cut off connection
Overcome the enemy: enhance "affinity" and cut off connection Facing the invasion of malaria parasites, how do antibodies defeat the enemy? In the study, the authors found that the LAIR1Ab mutation inserted by the antibody has a molecular mechanism of "enhancing affinity"
.
Gao Fu et al.
found that the RIFIN-LAIR1 interaction can cause signal activation downstream of the LAIR1 receptor; and public antibodies with LAIR1 Ab insertion, such as MGD21 and MGM5, can block the activation of downstream signals of LAIR1 caused by RIFIN
.
Ab "This reveals that the malaria parasite uses the RIFIN protein to interact with the immunosuppressive receptor LAIR1 to achieve immune escape
.
" Song Hao explained, "On the contrary, in response to the malaria parasite infection, the host produces a public antibody with LAIR1Ab inserted to block RIFIN.
-LAIR1 interaction
.
"
Based on this, the author revealed that Plasmodium falciparum uses the RIFIN protein on the surface of infected red blood cells to regulate host immune cell functions, elucidating the immune escape mechanism of Plasmodium falciparum, and the host performs immune countermeasures by producing public antibodies, indicating that the Plasmodium and the host are in A game mechanism based on RIFIN-LAIR1 has emerged in the long-term evolution process
.
"This study is a very elegant study to solve the problem of how RIFINs bind to LAIR1 and how the antibody containing LAIR1 works
.
It is a very good structural work
.
" Another reviewer commented
.
The research was supported by funds from the Strategic Leading Science and Technology Special Project of the Chinese Academy of Sciences , the National Science and Technology Major Project, and the Youth Promotion Association of the Chinese Academy of Sciences
.
(Source: Feng Lifei, China Science News)
Chinese Academy of Sciences Related paper information: https://doi.
org/10.
1016/j.
celrep.
2021.
109600
https://doi.
org/10.
1016/j.
celrep.
2021.
109600 https://doi.
org/10.
1016/j.
celrep.
2021.
109600
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