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

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Title: PIMMS43 is required for malaria parasite immune evasion and sporogonic development in the mosquito vector
Authors: Ukegbu, CV
Giorgalli, M
Tapanelli, S
Rona, LDP
Jaye, A
Wyer, C
Angrisano, F
Christophides, G
Vlachou, D
Item Type: Journal Article
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.
Issue Date: 31-Mar-2020
Date of Acceptance: 21-Feb-2020
URI: http://hdl.handle.net/10044/1/78049
DOI: 10.1073/pnas.1919709117
ISSN: 0027-8424
Publisher: National Academy of Sciences
Start Page: 7363
End Page: 7373
Journal / Book Title: Proceedings of the National Academy of Sciences of USA
Volume: 117
Issue: 13
Copyright Statement: © 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY, https://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Bill & Melinda Gates Foundation
Medical Research Council (MRC)
Funder's Grant Number: 093587/Z/10/Z
107983/Z/15/Z
OPP1158151
MR/N00227X/1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
malaria transmission
mosquito innate immunity
complement-like response
transmission blocking vaccines
mosquito population replacement
COMPLEMENT-LIKE PROTEIN
PLASMODIUM-FALCIPARUM
ANOPHELES-GAMBIAE
SURFACE PROTEIN
TRANSMISSION
STEPHENSI
PFS47
GENE
INFECTIONS
SELECTION
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
Animals
Humans
Anopheles
Plasmodium falciparum
Oocysts
Sporozoites
Malaria, Falciparum
Protozoan Proteins
Female
Host-Parasite Interactions
Immune Evasion
Mosquito Vectors
Publication Status: Published
Online Publication Date: 2020-03-12
Appears in Collections:Faculty of Natural Sciences