Significance of Mannose-Binding Lectin Deficiency and Nucleotide-Binding Oligomerization Domain 2 Polymorphisms in Staphylococcus aureus Bloodstream Infections: A Case-Control Study

Michael Osthoff; Hue Mun Au Yong; Melinda M Dean; Damon P Eisen

doi:10.1371/journal.pone.0076218

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Significance of Mannose-Binding Lectin Deficiency and Nucleotide-Binding Oligomerization Domain 2 Polymorphisms in Staphylococcus aureus Bloodstream Infections: A Case-Control Study

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Significance of Mannose-Binding Lectin Deficiency and Nucleotide-Binding Oligomerization Domain 2 Polymorphisms in Staphylococcus aureus Bloodstream Infections: A Case-Control Study

Michael Osthoff, Hue Mun Au Yong, Melinda M Dean and Damon P Eisen

PLoS One, Vol.8(9), pp.1-8

2013

DOI: https://doi.org/10.1371/journal.pone.0076218

PMID: 24927018

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Abstract

caspase recruitment domain protein 15

mannose binding lectin 2

bloodstream infection

disease severity

female

gene frequency

genetic association

genetic polymorphism

Background: Pathways 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 methods: A 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. Results: After 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). Conclusions: Contrary 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.

Details

Title: Significance of Mannose-Binding Lectin Deficiency and Nucleotide-Binding Oligomerization Domain 2 Polymorphisms in Staphylococcus aureus Bloodstream Infections: A Case-Control Study
Authors: Michael Osthoff (Author) - The Royal Melbourne Hospital
Hue Mun Au Yong (Author) - The Royal Melbourne Hospital
Melinda M Dean (Author) - Australian Red Cross Blood Service
Damon P Eisen (Author) - The Royal Melbourne Hospital
Publication details: PLoS One, Vol.8(9), pp.1-8
Publisher: Public Library of Science
Date published: 2013
DOI: 10.1371/journal.pone.0076218
ISSN: 1932-6203; 1932-6203
PMID: 24927018
Copyright note: © 2013 Osthoff et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Organisation Unit: School of Health - Biomedicine; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99513884002621
Output Type: Journal article

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