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Anopheles stephensi p38 MAPK signaling regulates innate immunity and bioenergetics during Plasmodium falciparum infection

Overview of attention for article published in Parasites & Vectors, August 2015
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Title
Anopheles stephensi p38 MAPK signaling regulates innate immunity and bioenergetics during Plasmodium falciparum infection
Published in
Parasites & Vectors, August 2015
DOI 10.1186/s13071-015-1016-x
Pubmed ID
Authors

Bo Wang, Nazzy Pakpour, Eleonora Napoli, Anna Drexler, Elizabeth K. K. Glennon, Win Surachetpong, Kong Cheung, Alejandro Aguirre, John M. Klyver, Edwin E. Lewis, Richard Eigenheer, Brett S. Phinney, Cecilia Giulivi, Shirley Luckhart

Abstract

Fruit flies and mammals protect themselves against infection by mounting immune and metabolic responses that must be balanced against the metabolic needs of the pathogens. In this context, p38 mitogen-activated protein kinase (MAPK)-dependent signaling is critical to regulating both innate immunity and metabolism during infection. Accordingly, we asked to what extent the Asian malaria mosquito Anopheles stephensi utilizes p38 MAPK signaling during infection with the human malaria parasite Plasmodium falciparum. A. stephensi p38 MAPK (AsP38 MAPK) was identified and patterns of signaling in vitro and in vivo (midgut) were analyzed using phospho-specific antibodies and small molecule inhibitors. Functional effects of AsP38 MAPK inhibition were assessed using P. falciparum infection, quantitative real-time PCR, assays for reactive oxygen species and survivorship under oxidative stress, proteomics, and biochemical analyses. The genome of A. stephensi encodes a single p38 MAPK that is activated in the midgut in response to parasite infection. Inhibition of AsP38 MAPK signaling significantly reduced P. falciparum sporogonic development. This phenotype was associated with AsP38 MAPK regulation of mitochondrial physiology and stress responses in the midgut epithelium, a tissue critical for parasite development. Specifically, inhibition of AsP38 MAPK resulted in reduction in mosquito protein synthesis machinery, a shift in glucose metabolism, reduced mitochondrial metabolism, enhanced production of mitochondrial reactive oxygen species, induction of an array of anti-parasite effector genes, and decreased resistance to oxidative stress-mediated damage. Hence, P. falciparum-induced activation of AsP38 MAPK in the midgut facilitates parasite infection through a combination of reduced anti-parasite immune defenses and enhanced host protein synthesis and bioenergetics to minimize the impact of infection on the host and to maximize parasite survival, and ultimately, transmission. These observations suggest that, as in mammals, innate immunity and mitochondrial responses are integrated in mosquitoes and that AsP38 MAPK-dependent signaling facilitates mosquito survival during parasite infection, a fact that may attest to the relatively longer evolutionary relationship of these parasites with their invertebrate compared to their vertebrate hosts. On a practical level, improved understanding of the balances and trade-offs between resistance and metabolism could be leveraged to generate fit, resistant mosquitoes for malaria control.

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Mendeley readers

The data shown below were compiled from readership statistics for 55 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 3 5%
United Kingdom 1 2%
India 1 2%
Thailand 1 2%
Unknown 49 89%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 20%
Researcher 9 16%
Other 5 9%
Student > Bachelor 5 9%
Professor > Associate Professor 5 9%
Other 9 16%
Unknown 11 20%
Readers by discipline Count As %
Agricultural and Biological Sciences 14 25%
Biochemistry, Genetics and Molecular Biology 8 15%
Immunology and Microbiology 4 7%
Medicine and Dentistry 3 5%
Computer Science 2 4%
Other 9 16%
Unknown 15 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 May 2016.
All research outputs
#18,423,683
of 22,824,164 outputs
Outputs from Parasites & Vectors
#4,226
of 5,463 outputs
Outputs of similar age
#191,843
of 266,176 outputs
Outputs of similar age from Parasites & Vectors
#85
of 124 outputs
Altmetric has tracked 22,824,164 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,463 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 266,176 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 124 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.