title: The role of human innate immune factors in nasal colonization by Staphylococcus aureus.
abstract: Staphylococcus aureus colonization of the human nares predisposes to sometimes severe auto-infection. To investigate whether genetic polymorphism affects the S. aureus carriage status, sequence variation in alpha-defensin and beta-defensin, and mannose-binding lectin (MBL) genes were determined for a group of volunteers (n=109) with known S. aureus nasal carriage status. DEFA1/3 expression was measured in a subset of the volunteers (n=32). None of the single nucleotide polymorphisms studied could clearly distinguish the (non) carriage groups. S. aureus carriers differed from non-carriers in baseline level of HNP1-3 peptide production (median: 218 versus 89mug/ml, P=0.016). No association between HNP1-3 levels and the individual sequence polymorphisms was documented. The combined copy numbers of DEFA1/A3 genes ranged from 5 to 23 per diploid genome. A linear correlation between combined copy numbers and HNP1-3 peptide concentrations in nasal secretions of non-carriers was noted (r(2)=0.8991). DEFA3 gene was absent in 25% of the individuals. MBL haplotype A was overrepresented in persistent S. aureus carriers (87% vs. 67%; P=0.038). In conclusion, defensin gene polymorphism, both in sequence and in gene copy numbers, does not seem to be involved in S. aureus carriage predisposition. However, MBL haplotypes do so significantly. Baseline HNP1-3 production is more the consequence of S. aureus colonization than a reason for the (non) carrier status.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Alex
authors.initials: A
authors.lastname: van Belkum
authors.forename: Marieke
authors.initials: M
authors.lastname: Emonts
authors.forename: Heiman
authors.initials: H
authors.lastname: Wertheim
authors.forename: Christa
authors.initials: C
authors.lastname: de Jongh
authors.forename: Jan
authors.initials: J
authors.lastname: Nouwen
authors.forename: Hans
authors.initials: H
authors.lastname: Bartels
authors.forename: Alexander
authors.initials: A
authors.lastname: Cole
authors.forename: Amy
authors.initials: A
authors.lastname: Cole
authors.forename: Peter
authors.initials: P
authors.lastname: Hermans
authors.forename: Hélène
authors.initials: H
authors.lastname: Boelens
authors.forename: Nicole Lemmens-den
authors.initials: NL
authors.lastname: Toom
authors.forename: Susan
authors.initials: S
authors.lastname: Snijders
authors.forename: Henri
authors.initials: H
authors.lastname: Verbrugh
authors.forename: Willem
authors.initials: W
authors.lastname: van Leeuwen
mesh_terms: D002353:Carrier State / Q000382:microbiology*; D018628:Gene Dosage; D006801:Humans; D007113:Immunity, Innate; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism; D009296:Nasal Cavity / Q000276:immunology / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D013211:Staphylococcus aureus / Q000254:growth & development*; D023084:alpha-Defensins / Q000235:genetics* / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics* / Q000378:metabolism
chemical_list: D037601:Mannose-Binding Lectin; D023084:alpha-Defensins; D023083:beta-Defensins; C406413:human neutrophil peptide 1