Staphylococcal protein A-formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps

J Allergy Clin Immunol. 2015 Aug;136(2):343-50.e8. doi: 10.1016/j.jaci.2014.10.058. Epub 2015 Feb 25.

Abstract

Background: Recent studies have revealed that Staphylococcus aureus and its components participate in the pathogenesis of eosinophilic airway diseases, such as chronic rhinosinusitis with nasal polyps.

Objective: We sought to determine whether staphylococcal protein A (SpA) from S aureus regulated cellular responses in nasal polyps, especially when coupled to immunoglobulins in immune complexes (ICs).

Methods: Dispersed nasal polyp cells (DNPCs) or peripheral blood monocytes were cultured in vitro with SpA in the presence or absence of IgG, and IL-5, IL-13, IFN-γ, IL-17A, and IL-10 levels were measured in the supernatants. The effect of SpA exposure on staphylococcal enterotoxin B-induced cytokine production by DNPCs in the presence and absence of IgG, IgA, and autologous serum was also examined.

Results: Exposure to SpA induced DNPCs to produce significantly higher IL-10, IL-13, and IL-17A levels than DNPCs without SpA, although the magnitude of the IL-17A increase was less than that of IL-10 and IL-13. SpA induced IL-10 production mainly from adherent DNPCs, and this was significantly enhanced in the presence of IgG; similar results were observed in peripheral blood monocytes. IC formation between SpA and IgG (SpA-IgG ICs) was confirmed by using native polyacrylamide gel electrophoresis. SpA-IgG ICs, but not SpA alone, almost completely suppressed staphylococcal enterotoxin B-induced IL-5, IL-13, IFN-γ, and IL-17A production by DNPCs; similar inhibition was observed in DNPCs treated with SpA in the presence of either IgA or autologous serum.

Conclusions: Our results suggest that SpA can regulate the pathogenesis of enterotoxin-induced inflammation in patients with chronic rhinosinusitis with nasal polyps through coupling to immunoglobulins.

Keywords: Chronic rhinosinusitis with nasal polyps; Staphylococcus aureus; cytokines; enterotoxins; immune complexes; immune evasion; immunoglobulins; staphylococcal protein A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigen-Antibody Complex / biosynthesis*
  • Case-Control Studies
  • Cell Adhesion / drug effects
  • Enterotoxins / antagonists & inhibitors
  • Enterotoxins / pharmacology*
  • Female
  • Humans
  • Immunoglobulin A / pharmacology
  • Immunoglobulin G / pharmacology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-13 / biosynthesis
  • Interleukin-13 / immunology
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / immunology
  • Interleukin-5 / biosynthesis
  • Interleukin-5 / immunology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / pathology
  • Male
  • Middle Aged
  • Nasal Cavity / immunology
  • Nasal Cavity / pathology
  • Nasal Cavity / surgery
  • Nasal Polyps / complications
  • Nasal Polyps / immunology*
  • Nasal Polyps / pathology
  • Nasal Polyps / surgery
  • Primary Cell Culture
  • Rhinitis / complications
  • Rhinitis / immunology*
  • Rhinitis / pathology
  • Rhinitis / surgery
  • Sinusitis / complications
  • Sinusitis / immunology*
  • Sinusitis / pathology
  • Sinusitis / surgery
  • Staphylococcal Protein A / pharmacology*

Substances

  • Antigen-Antibody Complex
  • Enterotoxins
  • IL17A protein, human
  • IL5 protein, human
  • Immunoglobulin A
  • Immunoglobulin G
  • Interleukin-13
  • Interleukin-17
  • Interleukin-5
  • Staphylococcal Protein A
  • enterotoxin B, staphylococcal
  • Interferon-gamma