Protection against <i>Neisseria meningitidis</i> nasopharyngeal colonization relies on antibody opsonization and phagocytosis by neutrophils
Notice bibliographique
Résumé
ABSTRACT Neisseria meningitidis is a human-restricted pathogen that can cause a rapidly progressing invasive meningococcal disease, yet it is also a regular inhabitant of the human nasopharynx. Vaccines that target N. meningitidis aim to prevent invasive disease, but their ability to interfere with nasal colonization could effectively eradicate this bacteria in a population, and so is an important target for meningococcal vaccine design. While protection against invasive meningococcal disease is classically attributed to IgG-dependent complement activation and bacterial killing, there remains no indication of what confers protection against nasopharyngeal colonization, making it impossible to deliberately target this stage during vaccine development. Moreover, without understanding what confers protection in this tissue site, it is impossible to understand the level of susceptibility within a population. To address this, we have taken advantage of the CEACAM1-humanized mouse model to characterize immune effectors that protect against nasal carriage of N. meningitidis . Protection against nasal colonization could be induced by live mucosal infection or by parenteral immunization with heat-killed bacteria. Mice possessing genetic deficiencies in B cells were used to evaluate the role of B cells and a specific antibody response, while neutrophil and complement depletion were used to evaluate their respective contributions to immunization-induced protection against meningococcal nasal carriage. Despite the essential role for complement killing in preventing invasive meningococcal disease, complement was not required for protection against nasal colonization. Instead, N. meningitidis- specific antibodies and neutrophils were both required to protect mice against the nasal infection. Combined, these data suggest that phagocytic bacterial killing is necessary for protection against mucosal colonization by N. meningitidis , indicating that nasal immunoglobulin with the ability to promote opsonophagocytosis must be considered as a correlate of protection against meningococcal carriage. AUTHOR’S SUMMARY Neisseria meningitidis can cause devastating and often fatal systemic infections including sepsis and meningitis, yet it frequently lives in the throat of healthy individuals. Vaccines developed against some meningococcal strains allow the individual to resist becoming colonized by the bacteria, an effect that protects them from disease and prevents them from spreading the bacteria to others, while other vaccines effectively protect against disease but still allow the individual to carry the bacteria in their throat. The reason for this difference has remained difficult to explain. Here, we use a ‘humanized’ mouse model that allows N. meningitidis infection in the nasal passages to establish that effective protection against nasal colonization requires that antibodies present within the infected mucosal tissues can coat the bacteria so that they are engulfed by neutrophils, a potent bacteria-killing white blood cell that is recruited to the site of infection. These findings suggest that antibodies with the ability to promote neutrophil recognition and killing of N. meningitidis should be the goal of future vaccines, and the presence of these can be used to consider an individual’s resistance against this terrible pathogen.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».