Repository logo
 

PIMMS43 is required for malaria parasite immune evasion and sporogonic development in the mosquito vector.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Ukegbu, Chiamaka V 
Giorgalli, Maria 
Tapanelli, Sofia 
Rona, Luisa DP 
Jaye, Amie 

Abstract

After being ingested by a female Anopheles mosquito during a bloodmeal on an infected host, and before they can reach the mosquito salivary glands to be transmitted to a new host, Plasmodium parasites must establish an infection of the mosquito midgut in the form of oocysts. To achieve this, they must first survive a series of robust innate immune responses that take place prior to, during, and immediately after ookinete traversal of the midgut epithelium. Understanding how parasites may evade these responses could highlight new ways to block malaria transmission. We show that an ookinete and sporozoite surface protein designated as PIMMS43 (Plasmodium Infection of the Mosquito Midgut Screen 43) is required for parasite evasion of the Anopheles coluzzii complement-like response. Disruption of PIMMS43 in the rodent malaria parasite Plasmodium berghei triggers robust complement activation and ookinete elimination upon mosquito midgut traversal. Silencing components of the complement-like system through RNAi largely restores ookinete-to-oocyst transition but oocysts remain small in size and produce a very small number of sporozoites that additionally are not infectious, indicating that PIMMS43 is also essential for sporogonic development in the oocyst. Antibodies that bind PIMMS43 interfere with parasite immune evasion when ingested with the infectious blood meal and significantly reduce the prevalence and intensity of infection. PIMMS43 genetic structure across African Plasmodium falciparum populations indicates allelic adaptation to sympatric vector populations. These data add to our understanding of mosquito-parasite interactions and identify PIMMS43 as a target of malaria transmission blocking.

Description

Keywords

complement-like response, malaria transmission, mosquito innate immunity, mosquito population replacement, transmission blocking vaccines, Animals, Anopheles, Female, Host-Parasite Interactions, Humans, Immune Evasion, Malaria, Falciparum, Mosquito Vectors, Oocysts, Plasmodium falciparum, Protozoan Proteins, Sporozoites

Journal Title

Proc Natl Acad Sci U S A

Conference Name

Journal ISSN

0027-8424
1091-6490

Volume Title

117

Publisher

Proceedings of the National Academy of Sciences
Sponsorship
Medical Research Council (MR/N00227X/1)