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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis
|
|---|---|
| Published in |
Frontiers in immunology, September 2017
|
| DOI | 10.3389/fimmu.2017.01127 |
| Pubmed ID | |
| Authors |
Áislan de Carvalho Vivarini, Teresa Cristina Calegari-Silva, Alessandra Mattos Saliba, Viviane Sampaio Boaventura, Jaqueline França-Costa, Ricardo Khouri, Tim Dierckx, Karina Luiza Dias-Teixeira, Nicolas Fasel, Aldina Maria Prado Barral, Valéria Matos Borges, Johan Van Weyenbergh, Ulisses Gazos Lopes |
| Abstract |
Leishmania parasites infect macrophages, causing a wide spectrum of human diseases, from cutaneous to visceral forms. In search of novel therapeutic targets, we performed comprehensive in vitro and ex vivo mapping of the signaling pathways upstream and downstream of antioxidant transcription factor [nuclear factor erythroid 2-related factor 2 (Nrf2)] in cutaneous leishmaniasis (CL), by combining functional assays in human and murine macrophages with a systems biology analysis of in situ (skin biopsies) CL patient samples. First, we show the PKR pathway controls the expression and activation of Nrf2 in Leishmania amazonensis infection in vitro. Nrf2 activation also required PI3K/Akt signaling and autophagy mechanisms. Nrf2- or PKR/Akt-deficient macrophages exhibited increased levels of ROS/RNS and reduced expression of Sod1 Nrf2-dependent gene and reduced parasite load. L. amazonensis counteracted the Nrf2 inhibitor Keap1 through the upregulation of p62 via PKR. This Nrf2/Keap1 observation was confirmed in situ in skin biopsies from Leishmania-infected patients. Next, we explored the ex vivo transcriptome in CL patients, as compared to healthy controls. We found the antioxidant response element/Nrf2 signaling pathway was significantly upregulated in CL, including downstream target p62. In silico enrichment analysis confirmed upstream signaling by interferon and PI3K/Akt, and validated our in vitro findings. Our integrated in vitro, ex vivo, and in silico approach establish Nrf2 as a central player in human cutaneous leishmaniasis and reveal Nrf2/PKR crosstalk and PI3K/Akt pathways as potential therapeutic targets. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 4 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Scientists | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 45 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 20% |
| Student > Master | 8 | 18% |
| Student > Bachelor | 4 | 9% |
| Professor > Associate Professor | 3 | 7% |
| Student > Doctoral Student | 2 | 4% |
| Other | 6 | 13% |
| Unknown | 13 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 7 | 16% |
| Biochemistry, Genetics and Molecular Biology | 7 | 16% |
| Immunology and Microbiology | 4 | 9% |
| Medicine and Dentistry | 2 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
| Other | 4 | 9% |
| Unknown | 20 | 44% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 03 October 2017.
All research outputs
#14,605,790
of 25,382,440 outputs
Outputs from Frontiers in immunology
#12,364
of 31,537 outputs
Outputs of similar age
#158,342
of 323,373 outputs
Outputs of similar age from Frontiers in immunology
#229
of 491 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 31,537 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has gotten more attention than average, scoring higher than 59% of its peers.
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 323,373 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 50% of its contemporaries.
We're also able to compare this research output to 491 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.