Malaria parasite Pfs47 disrupts JNK signaling to escape mosquito immunity

Smith, Ryan C.; Jacobs-­Lorena, Marcelo

doi:10.1073/pnas.1424227112

Cited by 7 publications

(4 citation statements)

References 11 publications

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“…These measurements are in accordance with the reported cell sizes ( 9 , 23 , 41 ). Similar to recent studies based on flow cytometry of fixed cells ( 23 , 41 ), we did not detect the cells of 2 µm in size described by other research groups based on label-free light microscopy alone ( 27 , 60 ). When comparing the cell groups in terms of bright-field measurements of their cytoplasm, PPO6 low cells showed smaller area, width, and minor axis than PPO6 high cells ( Fig.…”

Section: Resultssupporting

confidence: 91%

Unbiased classification of mosquito blood cells by single-cell genomics and high-content imaging

Severo

Landry

Lindquist

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceMosquito blood cells are central players of immunity against the vector-borne pathogens that devastate the lives of millions of people worldwide. However, their molecular identity and classification remain controversial. By applying single-cell RNA sequencing and high-content imaging flow cytometry, we defined the molecular fingerprint of a subset of mosquito blood cells and characterized two transcriptionally distinct blood cell populations that resemble previously described cell types. Surprisingly, cell population analyses at a single-cell level uncovered an active molecular transfer between the two cell types that may contribute to cellular diversity and plasticity seen across biological systems.

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Section: Resultssupporting

confidence: 91%

Unbiased classification of mosquito blood cells by single-cell genomics and high-content imaging

Severo

Landry

Lindquist

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…Understanding mechanisms of immune evasion could nevertheless provide novel opportunities for disease control, as illustrated by studies showing how Plasmodium avoids immune recognition by the mosquito midgut. During invasion 85,112 , ookinetes express the protein Pfs47 on their surface, which in some way makes them ‘invisible’ to the immune system, preventing nitration and activation of the complement-like cascades described earlier 113,114 . The global diversity of Pfs47 in Plasmodium isolates suggests that this mechanism has been selected for on a local scale in different Anopheles– Plasmodium combinations, with potential consequences for the global spread of malaria 115 .…”

Section: Interventions For Vector Controlmentioning

confidence: 99%

Vector biology meets disease control: using basic research to fight vector-borne diseases

2018

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Human pathogens that are transmitted by insects are a global problem, particularly those vectored by mosquitoes; for example, malaria parasites transmitted by Anopheles species, and viruses such as dengue, Zika and chikungunya that are carried by Aedes mosquitoes. Over the past 15 years, the prevalence of malaria has been substantially reduced and virus outbreaks have been contained by controlling mosquito vectors using insecticide-based approaches. However, disease control is now threatened by alarming rates of insecticide resistance in insect populations, prompting the need to develop a new generation of specific strategies that can reduce vector-mediated transmission. Here, we review how increased knowledge in insect biology and insect-pathogen interactions is stimulating new concepts and tools for vector control. We focus on strategies that either interfere with the development of pathogens within their vectors or directly impact insect survival, including enhancement of vector-mediated immune control, manipulation of the insect microbiome, or use of powerful new genetic tools such as CRISPR-Cas systems to edit vector genomes. Finally, we offer a perspective on the implementation hurdles as well as the knowledge gaps that must be filled in the coming years to safely realize the potential of these novel strategies to eliminate the scourge of vector-borne disease.

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“…A recent study revealed that Pfs47 mediates immune evasion in mosquitoes through interaction with the Anopheles midgut receptor protein AgPf47Rec (AGAP006398) 130 . The interaction allows the parasite to evade the mosquito immune system by disrupting the c-Jun-N-terminal kinase (JNK) signaling pathway and eventually suppressing the effect of midgut nitration, a crucial reaction to activate the mosquito complement-like system 68 , 69 , 109 , 131 , 132 . Further studies are needed to determine if antibodies against AgPfs47Rec possess TB activity.…”

Section: Midgut Protein Interactions Affecting Plasmodium Transmissionmentioning

confidence: 99%

Molecular interactions between parasite and mosquito during midgut invasion as targets to block malaria transmission

Keleta

Ramelow

2021

npj Vaccines

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Despite considerable effort, malaria remains a major public health burden. Malaria is caused by five Plasmodium species and is transmitted to humans via the female Anopheles mosquito. The development of malaria vaccines against the liver and blood stages has been challenging. Therefore, malaria elimination strategies advocate integrated measures, including transmission-blocking approaches. Designing an effective transmission-blocking strategy relies on a sophisticated understanding of the molecular mechanisms governing the interactions between the mosquito midgut molecules and the malaria parasite. Here we review recent advances in the biology of malaria transmission, focusing on molecular interactions between Plasmodium and Anopheles mosquito midgut proteins. We provide an overview of parasite and mosquito proteins that are either targets for drugs currently in clinical trials or candidates of promising transmission-blocking vaccines.

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Malaria parasite Pfs47 disrupts JNK signaling to escape mosquito immunity

Cited by 7 publications

References 11 publications

Unbiased classification of mosquito blood cells by single-cell genomics and high-content imaging

Unbiased classification of mosquito blood cells by single-cell genomics and high-content imaging

Vector biology meets disease control: using basic research to fight vector-borne diseases

Molecular interactions between parasite and mosquito during midgut invasion as targets to block malaria transmission

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