Structural basis of malarial parasite RIFIN-mediated immune escape against LAIR1
Yijia Xie,
Xin Li,
Yan Chai,
Hao Song,
Jianxun Qi,
George F. Gao
Affiliations
Yijia Xie
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
Xin Li
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
Yan Chai
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Hao Song
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding author
Jianxun Qi
University of Chinese Academy of Sciences, Beijing 100049, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Corresponding author
George F. Gao
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Influenza Research and Early Warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China; Corresponding author
Summary: Malaria infection by Plasmodium falciparum continues to pose a global threat to the human population. P. falciparum expresses variable erythrocyte surface antigens such as RIFINs. Public antibodies with LAIR1 insertion have been identified from malarial patients against a subset of RIFINs. In this study, we solve a LAIR1-binding RIFIN structure: the complex structures of two RIFINs bound to mutated or wild-type LAIR1 in two distinct patterns. Notably, the two RIFINs engage similar binding sites on LAIR1 with different angles, and the RIFIN-binding sites overlap with the collagen-binding site. Surprisingly, RIFINs use completely different binding sites to bind to LAIR1 or LILRB1, indicating the kaleidoscopic change of RIFINs. We then verify that RIFIN could induce LAIR1-mediated cell signaling, and LAIR1-containing antibodies could block the pathway. The findings of this study provide structural insights into the mechanism of the immune escape of P. falciparum and the endless arms race between parasite and host.
