title: MBL2 deficiency is associated with higher genomic bacterial loads during meningococcemia in young children.
abstract: Mannose binding lectin (MBL2) is a soluble pattern recognition receptor that is key to generating innate immune responses to invasive infection, including against the cardinal Gram-negative bacterium Neisseria meningitidis. Individuals homozygous or heterozygous for any of three variant alleles of MBL2 (O/O or A/O genotypes) have deficient concentrations of MBL2 in circulating blood, but previous studies linking MBL deficiency to susceptibility to meningococcal disease have not revealed a consistent association. We genotyped 741 patients with microbiologically-proven meningococcal disease and correlated MBL2 genotype with plasma bacterial load of N. meningitidis with blood samples taken during hospital admission. We show that individuals with genotypes compatible with MBL2 deficiency have higher measurable levels of bacterial plasma genomic load with the greatest effect seen in children <2 years of age. However, the overall impact of this is minor, because there was no evidence that such genotypes are more common in children with meningococcal disease compared with uninfected cohorts. The findings suggest that MBL2 supports innate immune defence against meningococcal disease in the early months of life, before acquired immunity is sufficiently robust for effective natural protection.
authors: Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; Department of Infection and Immunity, University of Sheffield, Sheffield, UK.
authors: T C
authors: TC
authors: Darton
authors: D L
authors: DL
authors: Jack
authors: M
authors: M
authors: Johnson
authors: R
authors: R
authors: Borrow
authors: M
authors: M
authors: Guiver
authors: E B
authors: EB
authors: Kaczmarski
authors: M W
authors: MW
authors: Turner
authors: N J
authors: NJ
authors: Klein
authors: R C
authors: RC
authors: Read
mesh_terms: D000293:Adolescent; D016470:Bacteremia / Q000235:genetics* / Q000276:immunology*; D058491:Bacterial Load; D001769:Blood / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007223:Infant; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency*; D008589:Meningococcal Infections / Q000235:genetics* / Q000276:immunology*; D008661:Metabolism, Inborn Errors; D009345:Neisseria meningitidis / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D037601:Mannose-Binding Lectin
keywords: Genomic bacterial load; Gram-negative sepsis; Neisseria meningitidis; mannose-binding lectin; meningococcal infection