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Chronic morphine and HIV-1 Tat promote differential central nervous system trafficking of CD3+ and Ly6C+ immune cells in a murine Streptococcus pneumoniae infection model

Overview of attention for article published in Journal of Neuroinflammation, June 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (75th percentile)
  • High Attention Score compared to outputs of the same age and source (80th percentile)

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8 tweeters

Citations

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12 Dimensions

Readers on

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28 Mendeley
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Title
Chronic morphine and HIV-1 Tat promote differential central nervous system trafficking of CD3+ and Ly6C+ immune cells in a murine Streptococcus pneumoniae infection model
Published in
Journal of Neuroinflammation, June 2015
DOI 10.1186/s12974-015-0341-5
Pubmed ID
Authors

Raini Dutta, Sabita Roy

Abstract

Persistent systemic infection results in excessive trafficking of peripheral immune cells into the central nervous system (CNS), thereby contributing to sustained neuroinflammation that leads to neurocognitive deficits. In this study, we explored the role of opportunistic systemic infection with Streptococcus pneumoniae in the recruitment of peripheral leukocytes into the CNS and its contribution to HIV-1-associated neurocognitive disorders in opioid-dependent individuals. Wild-type B6CBAF1 (wt), μ-opioid receptor knockout (MORKO), FVB/N luciferase transgenic, and Toll-like receptor 2 and 4 knockout (TLR2KO and TLR4KO) mice were subcutaneously implanted with morphine/placebo pellet followed by HIV-1 Transactivator of transcription (Tat) protein injection intravenously and S. pneumoniae administration intraperitoneally. On postoperative day 5, brains perfused with phosphate-buffered saline were harvested and subjected to immunohistochemistry (for bacterial trafficking and chemokine ligand generation), flow cytometry (for phenotypic characterization of CNS trafficked immune cells), Western blot, and real-time PCR (for ligand expression). Our results show differential leukocyte trafficking of T lymphocytes (CD3+) and inflammatory monocytes (Ly6C+) into the CNS of mice treated with morphine, HIV-1 Tat, and/or S. pneumoniae. In addition, we demonstrate a Trojan horse mechanism for bacterial dissemination across the blood-brain barrier into the CNS by monocytes. Activation of TLRs on microglia induced a chemokine gradient that facilitated receptor-dependent trafficking of peripheral immune cells into the CNS. HIV-1 Tat induced trafficking of Ly6C+ and CD3+ cells into the CNS; infection with S. pneumoniae facilitated infiltration of only T lymphocytes into the CNS. We also observed differential chemokine secretion in the CNS, with CCL5 being the predominant chemokine following HIV-1 Tat treatment, which was potentiated further with morphine. S. pneumoniae alone led to preferential induction of CXCL12. Furthermore, we attributed a regulatory role for TLRs in the chemokine-mediated trafficking of leukocytes into the CNS. Chronic morphine and HIV-1 Tat, in the context of systemic S. pneumoniae co-infection, differentially modulated induction of TLR2/4, which consequently facilitated trafficking of TLR2 → CD3 + CCR5+ and TLR4 → Ly6C+(CCR5+/CXCR4+) immune cells into the CNS. Our murine study suggests that secondary infection in opioid-dependent individuals infected with HIV-1 augments peripheral leukocyte trafficking as a consequence of sustained chemokine gradients in the CNS.

Twitter Demographics

The data shown below were collected from the profiles of 8 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 4%
Unknown 27 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 21%
Student > Master 4 14%
Researcher 4 14%
Other 3 11%
Student > Doctoral Student 2 7%
Other 7 25%
Unknown 2 7%
Readers by discipline Count As %
Medicine and Dentistry 7 25%
Agricultural and Biological Sciences 6 21%
Biochemistry, Genetics and Molecular Biology 3 11%
Immunology and Microbiology 3 11%
Computer Science 1 4%
Other 4 14%
Unknown 4 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 24 March 2016.
All research outputs
#2,684,771
of 11,631,546 outputs
Outputs from Journal of Neuroinflammation
#324
of 1,323 outputs
Outputs of similar age
#56,384
of 234,639 outputs
Outputs of similar age from Journal of Neuroinflammation
#9
of 46 outputs
Altmetric has tracked 11,631,546 research outputs across all sources so far. Compared to these this one has done well and is in the 76th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,323 research outputs from this source. They receive a mean Attention Score of 4.9. This one has done well, scoring higher than 75% 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 234,639 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 46 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.