Evidence map›Paper›PMID 29980196›Full record

ArticleJournal of neuroinflammation2018

Increased hypothalamic microglial activation after viral-induced pneumococcal lung infection is associated with excess serum amyloid A production.

Hao Wang, Melissa Blackall, Luba Sominsky, Sarah J Spencer, Ross Vlahos, Melissa Churchill, Steven Bozinovski

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Hao WangSchool of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia.
Melissa BlackallSchool of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia.
Luba SominskySchool of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia.
Sarah J SpencerSchool of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia.
Ross VlahosSchool of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia.
Melissa ChurchillSchool of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia.
Steven BozinovskiSchool of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia. steven.bozinovski@rmit.edu.au.
RMIT University · AU

Funding

Australian Research Council FT130100654National Health and Medical Research Council APP1067547
6 · The paper itself

Abstract

backgroundIt is well established that lung pathology and inflammation are more severe during respiratory infections complicated by the presence of both bacteria and viruses. Whilst co-infection can result in invasive pneumococcal disease and systemic inflammation, the neuroinflammatory consequences of co-infection are poorly characterised.

methodsIn this study, we utilised a mouse co-infection model involving Streptococcus pneumoniae (S. pneumoniae) and influenza A virus (IAV) lung infection, and we also isolated microglia for ex vivo stimulation with pneumococcus or serum amyloid A (SAA).

resultsCo-infection but not S. pneumoniae or IAV alone significantly increased the number of amoeboid-shaped microglia and expression of pro-inflammatory cytokines including tumour necrosis factor α (TNFα), interleukin-1β (IL-1β), interleukin-6 (IL-6), and C-C motif chemokine ligand-2 (CCL-2) in the hypothalamus. Pneumococcus was only detected in the hypothalamus of co-infected mice. In addition, the systemic inflammatory cytokines TNFα, IL-1β and IL-6 were not elevated in co-infected mice relative to IAV-infected mice, whereas SAA levels were markedly increased in co-infected mice (p < 0.05). SAA and its functional receptor termed formyl peptide receptor 2 (Fpr2) transcript expression were also increased in the hypothalamus. In mouse primary microglia, recombinant SAA but not S. pneumoniae stimulated TNFα, IL-1β, IL-6 and CCL-2 expression, and this response was completely blocked by the pro-resolving Fpr2 agonist aspirin-triggered resolvin D1 (AT-RvD1).

conclusionsIn summary, lung co-infection increased the number of 'activated' amoeboid-shaped microglia and inflammatory cytokine expression in the hypothalamus. Whilst persistent pneumococcal brain infection was observed, SAA proved to be a much more potent stimulus of microglia than pneumococci, and this response was potently suppressed by the anti-inflammatory AT-RvD1. Targeting Fpr2 with pro-resolving eicosanoids such as AT-RvD1 may restore microglial homeostasis during severe respiratory infections.

Indexed as

Amyloid beta-PeptidesAnimalsCalcium-Binding ProteinsCytokinesDisease Models, AnimalGlial Fibrillary Acidic ProteinHumansHypothalamusInfluenza A virusInfluenza, HumanMaleMiceMice, Inbred C57BLMicrofilament ProteinsMicrogliaPneumonia, PneumococcalAif1 protein, mouseAmyloid beta-PeptidesCalcium-Binding ProteinsCytokinesGlial Fibrillary Acidic ProteinMicrofilament ProteinsRNA, MessengerTumor Necrosis Factor-alphaMicrogliaNeuroinflammationPneumoniaResolvin-D1Serum amyloid A

Identifiers

PMID29980196
PMCPMC6035471
OpenAlexW2877578287

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.