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CD14hiCD16+ monocytes phagocytose antibody-opsonised Plasmodium falciparum infected erythrocytes more efficiently than other monocyte subsets, and require CD16 and complement to do so

Overview of attention for article published in BMC Medicine, July 2015
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  • Good Attention Score compared to outputs of the same age (69th percentile)

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Title
CD14hiCD16+ monocytes phagocytose antibody-opsonised Plasmodium falciparum infected erythrocytes more efficiently than other monocyte subsets, and require CD16 and complement to do so
Published in
BMC Medicine, July 2015
DOI 10.1186/s12916-015-0391-7
Pubmed ID
Authors

Jingling Zhou, Gaoqian Feng, James Beeson, P. Mark Hogarth, Stephen J. Rogerson, Yan Yan, Anthony Jaworowski

Abstract

With more than 600,000 deaths from malaria, mainly of children under five years old and caused by infection with Plasmodium falciparum, comes an urgent need for an effective anti-malaria vaccine. Limited details on the mechanisms of protective immunity are a barrier to vaccine development. Antibodies play an important role in immunity to malaria and monocytes are key effectors in antibody-mediated protection by phagocytosing antibody-opsonised infected erythrocytes (IE). Eliciting antibodies that enhance phagocytosis of IE is therefore an important potential component of an effective vaccine, requiring robust assays to determine the ability of elicited antibodies to stimulate this in vivo. The mechanisms by which monocytes ingest IE and the nature of the monocytes which do so are unknown. Purified trophozoite-stage P. falciparum IE were stained with ethidium bromide, opsonised with anti-erythrocyte antibodies and incubated with fresh whole blood. Phagocytosis of IE and TNF production by individual monocyte subsets was measured by flow cytometry. Ingestion of IE was confirmed by imaging flow cytometry. CD14(hi)CD16+ monocytes phagocytosed antibody-opsonised IE and produced TNF more efficiently than CD14(hi)CD16- and CD14(lo)CD16+ monocytes. Blocking experiments showed that Fcγ receptor IIIa (CD16) but not Fcγ receptor IIa (CD32a) or Fcγ receptor I (CD64) was necessary for phagocytosis. CD14(hi)CD16+ monocytes ingested antibody-opsonised IE when peripheral blood mononuclear cells were reconstituted with autologous serum but not heat-inactivated autologous serum. Antibody-opsonised IE were rapidly opsonised with complement component C3 in serum (t1/2 = 2-3 minutes) and phagocytosis of antibody-opsonised IE was inhibited in a dose-dependent manner by an inhibitor of C3 activation, compstatin. Compared to other monocyte subsets, CD14(hi)CD16+ monocytes expressed the highest levels of complement receptor 4 (CD11c) and activated complement receptor 3 (CD11b) subunits. We show a special role for CD14(hi)CD16+ monocytes in phagocytosing opsonised P. falciparum IE and production of TNF. While ingestion was mediated by Fcγ receptor IIIa, this receptor was not sufficient to allow phagocytosis; despite opsonisation with antibody, phagocytosis of IE also required complement opsonisation. Assays which measure the ability of vaccines to elicit a protective antibody response to P. falciparum should consider their ability to promote phagocytosis and fix complement.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 84 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Indonesia 1 1%
Brazil 1 1%
United Kingdom 1 1%
Canada 1 1%
Spain 1 1%
Unknown 79 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 20%
Researcher 15 18%
Student > Master 12 14%
Student > Bachelor 12 14%
Student > Doctoral Student 6 7%
Other 8 10%
Unknown 14 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 21 25%
Immunology and Microbiology 20 24%
Medicine and Dentistry 9 11%
Biochemistry, Genetics and Molecular Biology 7 8%
Computer Science 2 2%
Other 7 8%
Unknown 18 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 01 January 2016.
All research outputs
#6,968,736
of 23,302,246 outputs
Outputs from BMC Medicine
#2,525
of 3,507 outputs
Outputs of similar age
#79,311
of 263,334 outputs
Outputs of similar age from BMC Medicine
#62
of 74 outputs
Altmetric has tracked 23,302,246 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 3,507 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 43.7. This one is in the 27th percentile – i.e., 27% 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 263,334 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 74 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.