Evidence map›Paper›PMID 33004694›Full record

ArticleJCI insight2020

IsdB antibody-mediated sepsis following S. aureus surgical site infection.

Kohei Nishitani, Masahiro Ishikawa, Yugo Morita, Noriaki Yokogawa, Chao Xie, Karen L de Mesy Bentley, Hiromu Ito, Stephen L Kates, John L Daiss, Edward M Schwarz

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Host-Bacterium Interaction Mechanisms inInternational journal of molecular sciences · 2023
    Pooled it
  2. Osteomyelitis.Nature reviews. Disease primers · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Scaffold vaccination for prevention of orthopedic device infection.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Immune Checkpoint Molecules as Biomarkers ofbioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. The 2023 Orthopaedic Research Society's International Consensus Meeting on musculoskeletal infection: Summary from the host immunity section.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2024
    Article
  10. Article
  11. Article
  12. Fracture-related infection.Nature reviews. Disease primers · 2022
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Immune Response to Persistent Staphyloccocus Aureus Periprosthetic Joint Infection in a Mouse Tibial Implant Model.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
    Article
  18. International journal of molecular sciences · 2022
    Review
  19. Frontiers in cellular and infection microbiology · 2022
    Review
  20. Article
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

10 authors at 3 institutions in 2 countries.

Kohei NishitaniCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
Masahiro IshikawaCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
Yugo MoritaCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
Noriaki YokogawaCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
Chao XieCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
Karen L de Mesy BentleyCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
Hiromu ItoDepartment of Orthopaedic Surgery, Kyoto University, Kyoto, Japan.
Stephen L KatesDepartment of Orthopaedic Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
John L DaissCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
Edward M SchwarzCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
University of Rochester Medical Center · USKyoto University Hospital · JPVirginia Commonwealth University Medical Center · US

Funding

Research Supplement to Promote Diversity in Health Related ResearchUL1TR002649 · NCATS · VIRGINIA COMMONWEALTH UNIVERSITY · PI MOELLER, FREDERICK GERARD · 2018 to 2022
$19.1M
Project 2: Defining the Protective vs. Susceptible Immune Proteome of S. aureus OsteomyelitisP50AR072000 · NIAMS · UNIVERSITY OF ROCHESTER · PI Edward M. Schwarz · 2017 to 2026
$13.6M
Rochester Resource-Based Center for Bone, Muscle and Orthopaedic Research (ROCSTARR) (Overall Application)P30AR069655 · NIAMS · UNIVERSITY OF ROCHESTER · PI Edward M. Schwarz · 2016 to 2026
$7.8M
Diagnosis of early Staphylococcus aureus infections using circulating plasmablastsR21AI119646 · NIAID · UNIVERSITY OF ROCHESTER · PI DAISS, JOHN LINFORTH · 2016 to 2017
$422k
S. aureus Colonization of the Osteocytic-Canalicular Network in Diabetic Foot UlcersR21AR073321 · NIAMS · UNIVERSITY OF ROCHESTER · PI OH, IRVIN · 2018 to 2019
$373k
NCATS NIH HHS UL1 TR002649NIAID NIH HHS R21 AI119646NIAMS NIH HHS P30 AR069655NIAMS NIH HHS P50 AR072000NIAMS NIH HHS R21 AR073321
6 · The paper itself

Abstract

Staphylococcus aureus is prevalent in surgical site infections (SSI) and leads to death in approximately 1% of patients. Phase IIB/III clinical trial results have demonstrated that vaccination against the iron-regulated surface determinant protein B (IsdB) is associated with an increased mortality rate in patients with SSI. Thus, we hypothesized that S. aureus induces nonneutralizing anti-IsdB antibodies, which facilitate bacterial entry into leukocytes to generate "Trojan horse" leukocytes that disseminate the pathogen. Since hemoglobin (Hb) is the primary target of IsdB, and abundant Hb-haptoglobin (Hb-Hp) complexes in bleeding surgical wounds are normally cleared via CD163-mediated endocytosis by macrophages, we investigated this mechanism in vitro and in vivo. Our results demonstrate that active and passive IsdB immunization of mice renders them susceptible to sepsis following SSI. We also found that a multimolecular complex containing S. aureus protein A-anti-IsdB-IsdB-Hb-Hp mediates CD163-dependent bacterial internalization of macrophages in vitro. Moreover, IsdB-immunized CD163-/- mice are resistant to sepsis following S. aureus SSI, as are normal healthy mice given anti-CD163-neutralizing antibodies. These genetic and biologic CD163 deficiencies did not exacerbate local infection. Thus, anti-IsdB antibodies are a risk factor for S. aureus sepsis following SSI, and disruption of the multimolecular complex and/or CD163 blockade may intervene.

Indexed as

AnimalsAntibodies, BacterialAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, MyelomonocyticCation Transport ProteinsCD163 AntigenFemaleHaptoglobinsHemoglobinsMiceMice, Inbred BALB CMice, Inbred C57BLReceptors, Cell SurfaceSepsisStaphylococcal InfectionsAntibodies, BacterialAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, MyelomonocyticCation Transport ProteinsCD163 AntigenHaptoglobinsHemoglobinsIsdB protein, Staphylococcus aureusReceptors, Cell SurfaceBacterial infectionsBacterial vaccinesBone BiologyInfectious disease

Identifiers

PMID33004694
PMCPMC7566716
OpenAlexW3091075366

What OpenQuestion holds

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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.