Evidence map›Paper›PMID 25015832›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2014

Inhibition of the classical pathway of complement by meningococcal capsular polysaccharides.

Sarika Agarwal, Shreekant Vasudhev, Rosane B DeOliveira, Sanjay Ram

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Frontiers in cellular and infection microbiology · 2025
    Review
  4. Review
  5. Article
  6. The Host-Pathogen Interactions and Epicellular Lifestyle ofFrontiers in cellular and infection microbiology · 2022
    Review
  7. Pathogenic determinants ofFrontiers in pediatrics · 2022
    Review
  8. Review
  9. Frontiers in immunology · 2020
    Article
  10. Sepsis: mechanisms of bacterial injury to the patient.Scandinavian journal of trauma, resuscitation and emergency medicine · 2019
    Review
  11. Meningococcal pneumonia: a review.Pneumonia (Nathan Qld.) · 2019
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Regulation of capsule in Neisseria meningitidis.Critical reviews in microbiology · 2016
    Review
  17. Article
  18. Article
  19. Article
  20. Review
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

4 authors at 1 institution in 1 country.

Sarika AgarwalDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester MA 01605.
Shreekant VasudhevDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester MA 01605.
Rosane B DeOliveiraDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester MA 01605.
Sanjay RamDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester MA 01605 sanjay.ram@umassmed.edu.
University of Massachusetts Chan Medical School · US

Funding

The TLR4/MD-2 signaling pathway in gonoccocal diseaseU19AI084048 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI REED, GEORGE W. · 2009 to 2013
$13.1M
Immunology of Infection with Neisseria gonorrhoeaeR37AI032725 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RICE, PETER A. · 2004 to 2013
$6.1M
Complement Activation on Neisseria meningitidisR01AI054544 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RAM, SANJAY · 2004 to 2014
$3.4M
IMMUNOLOGY OF INFECTION WITH NEISSERIA GONORRHOEAER01AI032725 · NIAID · BOSTON MEDICAL CENTER · PI RICE, PETER A. · 1993 to 2003
$1.8M
Immunology of Infection with Neisseria gonorrhoeaeR56AI032725 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RAM, SANJAY, RICE, PETER A. · 2014 to 2014
$583k
Novel immunotherapeutics against multi-drug resistant Neisseria gonorrhoeaeR21AI111728 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RAM, SANJAY, SHAUGHNESSY, JUTAMAS · 2014 to 2015
$460k
NIAID NIH HHS AI054544NIAID NIH HHS AI084048NIAID NIH HHS AI32725NIAID NIH HHS R01 AI032725NIAID NIH HHS R01 AI054544NIAID NIH HHS R21 AI111728NIAID NIH HHS R37 AI032725NIAID NIH HHS R56 AI032725NIAID NIH HHS U19 AI084048
6 · The paper itself

Abstract

Almost all invasive Neisseria meningitidis isolates express capsular polysaccharide. Ab is required for complement-dependent killing of meningococci. Although alternative pathway evasion has received considerable attention, little is known about classical pathway (CP) inhibition by meningococci, which forms the basis of this study. We engineered capsulated and unencapsulated isogenic mutant strains of groups A, B, C, W, and Y meningococci to express similar amounts of the same factor H-binding protein (fHbp; a key component of group B meningococcal vaccines) molecule. Despite similar anti-fHbp mAb binding, significantly less C4b was deposited on all five encapsulated mutants compared with their unencapsulated counterparts (p < 0.01) when purified C1 and C4 were used to deposit C4b. Reduced C4b deposition was the result of capsule-mediated inhibition of C1q engagement by Ab. C4b deposition correlated linearly with C1q engagement by anti-fHbp. Whereas B, C, W, and Y capsules limited CP-mediated killing by anti-fHbp, the unencapsulated group A mutant paradoxically was more resistant than its encapsulated counterpart. Strains varied considerably in their susceptibility to anti-fHbp and complement despite similar Ab binding, which may have implications for the activity of fHbp-based vaccines. Capsule also limited C4b deposition by anti-porin A mAbs. Capsule expression decreased binding of an anti-lipooligosaccharide IgM mAb (∼ 1.2- to 2-fold reduction in fluorescence). Akin to observations with IgG, capsule also decreased IgM-mediated C4b deposition when IgM binding to the mutant strain pairs was normalized. In conclusion, we show that capsular polysaccharide, a critical meningococcal virulence factor, inhibits the CP of complement.

Indexed as

Immune EvasionAntibodies, MonoclonalAntigens, BacterialBacterial CapsulesBacterial ProteinsComplement C1qComplement C4bComplement Pathway, ClassicalHumansImmunoglobulin GImmunoglobulin MLipopolysaccharidesNeisseria meningitidisPorinsAntibodies, MonoclonalAntigens, BacterialBacterial Proteinscapsular polysaccharide, meningococcal group BComplement C1qComplement C4bfactor H-binding protein, Neisseria meningitidisImmunoglobulin GImmunoglobulin Mlipid-linked oligosaccharidesLipopolysaccharidesPorins

Identifiers

PMID25015832
PMCPMC4119509
OpenAlexW2109839957

What OpenQuestion holds

Textmetadata
LicenceTDM
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.