Glucose-based dialysis fluids inhibit innate defense against Staphylococcus aureus

Parvathi S. Kumar, Clifford T. Mauriello, Pamela S. Hair, Nicholas S. Rister, Courtney Lawrence, Reem H. Raafat, Kenji M. Cunnion

Research output: Contribution to journalArticle

Abstract

Background: Staphylococcus aureus peritonitis is a serious complication of Chronic Peritoneal Dialysis (CPD) and associated with a higher risk for severe and recurrent infections compared with other bacteria. We have previously shown that complement-mediated effectors essential for optimal opsonophagocytosis of S. aureus are inhibited by high glucose concentrations. Since most commonly used peritoneal dialysis (PD) fluids are glucose-based, we hypothesized that glucose-based PD fluids likely inhibit complement host defenses against S. aureus. Methods: Commercially available PD fluids were tested: glucose-based (Dianeal), Dianeal supplemented with amino acids, icodextrin-based (Extraneal) and amino acid-based (Nutrineal). Control PD fluid was generated to simulate Dianeal excluding the glucose. Three commercially available glucose concentrations were tested: Dianeal 1.5% (15gm/1000. ml), Dianeal 2.5% (25. gm/1000. ml) and Dianeal 4.25% (42.5. gm/1000. ml). Complement effectors against S. aureus were analyzed including opsonization with C3-fragments, anaphylatoxin generation, and phagocytosis efficiency. We also evaluated clinical strains, including MRSA strains, and specific complement activation pathways. Results: Glucose-based PD fluids inhibited complement opsonization of S. aureus (≥7-fold reduction) and inhibited S. aureus-induced generation of anaphylatoxins C3a and C5a (>10-fold reduction) compared to non-glucose based PD fluids. Dianeal 1.5%, 2.5% and 4.25%, all similarly inhibited C3-mediated opsonization. Glucose-based PD fluids showed a ≥4-fold reduction in opsonization of clinical strains of S.aureus, including MRSA strains. Decreased opsonization of S. aureus in the glucose-based PD fluid compared with non-glucose based fluids correlated with decreased phagocytosis by neutrophils. Conclusion: Complement-mediated opsonophagocytosis of S. aureus and anaphylatoxin generation were severely inhibited in glucose-based PD fluids compared with non-glucose-based PD fluids. By inhibiting complement host defenses, glucose-based PD fluids may increase the risk of and severity of S. aureus peritonitis for CPD patients using these fluids.

Original languageEnglish (US)
Pages (from-to)575-583
Number of pages9
JournalMolecular Immunology
Volume67
Issue number2
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Keywords

  • Anaphylatoxins
  • Complement
  • Opsonophagocytosis
  • Peritoneal dialysis
  • Peritonitis
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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  • Cite this

    Kumar, P. S., Mauriello, C. T., Hair, P. S., Rister, N. S., Lawrence, C., Raafat, R. H., & Cunnion, K. M. (2015). Glucose-based dialysis fluids inhibit innate defense against Staphylococcus aureus. Molecular Immunology, 67(2), 575-583. https://doi.org/10.1016/j.molimm.2015.07.017