Skip to main content

Volume 16 Supplement 3

Sepsis 2012

  • Poster presentation
  • Open access
  • Published:

Mannose-binding lectin deficiency and NOD2 mutations do not predispose to Staphylococcus aureus bloodstream infections but may influence outcome

Background

Staphylococcus aureus is a major cause of bloodstream infections (BSI), and is associated with a higher morbidity and mortality compared with other BSI pathogens. Innate pattern recognition receptors like mannose-binding lectin (MBL) of the complement system and NOD2 (nucleotide-binding oligomerization domain-containing protein 2), an intracellular sensor for a variety of pathogens, have been shown to be crucially involved in the immune response against S. aureus in knockout animal models [1, 2], but human data are lacking. Low MBL levels and NOD2 mutations can be found in up to 30% and 10% in the general population, respectively [3, 4]. This study aimed to investigate whether MBL deficiency and NOD2 mutations predispose to and influence the severity of S. aureus BSI.

Methods

A matched case-control study was undertaken involving 70 patients with S. aureus BSI and 70 age-matched and sex-matched hospitalized controls recruited prospectively at two major tertiary hospitals. Participant blood samples were analyzed for MBL levels by mannan-binding ELISA and for four MBL2 and three NOD2 polymorphisms by real-time PCR. Clinical and microbiological data were reviewed. MBL deficiency was defined as functional MBL level ≤0.1 μg/ml. Univariate and multivariate conditional logistic regression was used to investigate the risk of BSI in matched controls and cases.

Results

S. aureus BSI were nosocomially acquired (60%) and intravenous catheter associated (50%) in the majority of cases with an in-hospital mortality of 10%. After adjusting for diabetes, immunosuppression, chronic kidney disease and long-term intravenous catheters, MBL deficiency was found less frequently in cases than controls (8.6% vs. 20%, OR = 0.38, P = 0.07) as were low-producing MBL genotypes (11% vs. 23%, OR = 0.37, P = 0.05), whereas NOD2 polymorphisms were similarly distributed (14% vs. 10%, P = 0.4). In line with MBL2 genotypic results, MBL levels were significantly higher in cases than in controls (adjusted OR = 1.35 per 1 μg/ml increase, P = 0.002; Figure 1). Cases with NOD2 polymorphisms had less severe disease manifestations as shown by a lower SOFA score (mean 2.1 vs. 4.4, P = 0.04) and a reduced rate of multiorgan dysfunction and death (40% vs. 60%, P = 0.06), whereas MBL deficiency had no influence on the severity of S. aureus BSI.

Figure 1
figure 1

Differences in MBL serum concentrations in cases ( S. aureus BSI) and controls. Horizontal lines represent medians.

Conclusion

Neither MBL deficiency nor NOD2 polymorphisms were associated with an increased risk of S. aureus BSI. In fact, contrary to experimental data, MBL deficiency seemed to confer protection in acquiring S. aureus BSI, and NOD2 mutations were less frequently associated with multiorgan dysfunction in this matched case-control study.

References

  1. Deshmukh HS, Hamburger JB, Ahn SH, McCafferty DG, Yang SR, Fowler VG Jr: Critical role of NOD2 in regulating the immune response to Staphylococcus aureus . Infect Immun 2009, 77: 1376-1382. 10.1128/IAI.00940-08

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Ip WK, Takahashi K, Moore KJ, Stuart LM, Ezekowitz RA: Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome. J Exp Med 2008, 205: 169-181. 10.1084/jem.20071164

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Eisen DP, Dean MM, Boermeester MA, Fidler KJ, Gordon AC, Kronborg G, Kun JF, Lau YL, Payeras A, Valdimarsson H, et al.: Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection. Clin Infect Dis 2008, 47: 510-516. 10.1086/590006

    Article  PubMed  Google Scholar 

  4. Hugot JP, Zaccaria I, Cavanaugh J, Yang H, Vermeire S, Lappalainen M, Schreiber S, Annese V, Jewell DP, Fowler EV, et al.: Prevalence of CARD15/NOD2 mutations in Caucasian healthy people. Am J Gastroenterol 2007, 102: 1259-1267. 10.1111/j.1572-0241.2007.01149.x

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article

Osthoff, M., Au Yong, H., Dean, M. et al. Mannose-binding lectin deficiency and NOD2 mutations do not predispose to Staphylococcus aureus bloodstream infections but may influence outcome. Crit Care 16 (Suppl 3), P72 (2012). https://doi.org/10.1186/cc11759

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/cc11759

Keywords