Abstract
BackgroundPathways coordinated by innate pattern recognition receptors like mannose-binding lectin (MBL) and nucleotide-binding oligomerization domain 2 (NOD2) are among the first immune responses to Staphylococcus aureus (S. aureus) bloodstream infections (BSI) in animal models, but human data are limited. Here, we investigated the role of MBL deficiency and NOD2 mutations in the predisposition to and severity of S. aureus BSI.Patients and MethodsA matched case-control study was undertaken involving 70 patients with S. aureus BSI and 70 age- and sex-matched hospitalized controls. MBL levels, MBL2 and NOD2 polymorphisms were analyzed.ResultsAfter adjusting for potential confounders, MBL deficiency (<0.5 µg/ml) was found less frequently in cases than controls (26 vs. 41%, OR 0.4, 95% confidence interval (CI) 0.20-0.95, p=0.04) as were low producing MBL genotypes (11 vs. 23%, OR 0.2, 95% CI 0.08-0.75, p=0.01), whereas NOD2 polymorphisms were similarly distributed. Cases with NOD2 polymorphisms had less organ dysfunction as shown by a lower SOFA score (median 2.5 vs. 4.5, p=0.02), whereas only severe MBL deficiency (<0.1 µg/ml) was associated with life-threatening S. aureus BSI (OR 5.6, 95% CI 1.25-24.85, p=0.02).ConclusionsContrary to animal model data, our study suggests MBL deficiency may confer protection against acquiring S. aureus BSI. NOD2 mutations were less frequently associated with multi-organ dysfunction. Further human studies of the innate immune response in S. aureus BSI are needed to identify suitable host targets in sepsis treatment.
Highlights
Staphylococcus aureus (S. aureus) is a major cause of nosocomial and community-acquired bloodstream infections (BSI) accounting for up to 20% of hospital isolates [1]
In terms of risk factors, S. aureus BSI cases were more likely to suffer from liver disease, to require hemodialysis and to have long-term IV lines when compared to controls (Table 2)
Despite previous experimental studies that were the basis for our a priori hypotheses, we did not demonstrate that mannose-binding lectin (MBL) deficiency or nucleotide-binding oligomerization domain 2 (NOD2) mutations predispose to S. aureus BSI
Summary
Staphylococcus aureus (S. aureus) is a major cause of nosocomial and community-acquired bloodstream infections (BSI) accounting for up to 20% of hospital isolates [1]. MBL is able to bind to S. aureus [19] and evidence from animal models suggests that MBL deficiency significantly increases the susceptibility to and severity of S. aureus bacteremia [20,21]. Several clinical studies have reported a correlation between MBL deficiency and increased susceptibility to bacterial sepsis in children and adults [25,26,27]. Given these data on the potential role of NOD2 and MBL in human innate immune defences against severe S. aureus infection we hypothesized that MBL deficiency and NOD2 mutations might be associated with increased susceptibility to and severity of S. aureus BSI
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