Secreted aspartic protease 2 of Candida albicans inactivates factor H and the macrophage factor H-receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18)

Eliška Svoboda, Andrea E. Schneider, Noémi Sándor, Ulrich Lermann, Peter Staib, Mariann Kremlitzka, Zsuzsa Bajtay, Dagmar Barz, Anna Erdei, Mihály Józsi

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20 Citations (Scopus)

Abstract

The opportunistic pathogenic yeast Candida albicans employs several mechanisms to interfere with the human complement system. This includes the acquisition of host complement regulators, the release of molecules that scavenge complement proteins or block cellular receptors, and the secretion of proteases that inactivate complement components. Secreted aspartic protease 2 (Sap2) was previously shown to cleave C3b, C4b and C5. C. albicans also recruits the complement inhibitor factor H (FH), but yeast-bound FH can enhance the antifungal activity of human neutrophils via binding to complement receptor type 3 (CR3). In this study, we characterized FH binding to human monocyte-derived macrophages. Inhibition studies with antibodies and siRNA targeting CR3 (CD11b/CD18) and CR4 (CD11c/CD18), as well as analysis of colocalization of FH with these integrins indicated that both function as FH receptors on macrophages. Preincubation of C. albicans yeast cells with FH induced increased production of IL-1β and IL-6 in macrophages. Furthermore, FH enhanced zymosan-induced production of these cytokines. C. albicans Sap2 cleaved FH, diminishing its complement regulatory activity, and Sap2-treatment resulted in less detectable CR3 and CR4 on macrophages. These data show that FH enhances the activation of human macrophages when bound on C. albicans. However, the fungus can inactivate both FH and its receptors on macrophages by secreting Sap2, which may represent an additional means for C. albicans to evade the host innate immune system.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalImmunology letters
Volume168
Issue number1
DOIs
Publication statusPublished - Nov 1 2015

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Keywords

  • CR3
  • Candida albicans
  • Complement
  • Factor H
  • Fungal pathogen
  • Immune evasion
  • Protease
  • Sap2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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