Influence of Mannan and Glucan on Complement Activation and C3 Binding by<i>Candida albicans</i>

Boxx, Gayle M.; Kozel, Thomas R.; Nishiya, Casey T.; Zhang, Mason X.

doi:10.1128/iai.00744-09

Cited by 26 publications

(31 citation statements)

References 53 publications

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“…The published observations of efficient yeast cells opsonophagocytosis revealed ability of mannan-specific antibodies alone to serve as sufficient opsonins [34]. These results are supported by an earlier report of C. albicans yeast cells opsonophagocytic killing by human neutrophils induced by natural antimannan antibodies [35].…”

Section: Discussionsupporting

confidence: 80%

Effect of Branched α‐Oligomannoside Structures on Induction of Anti‐Candida Humoral Immune Response

Paulovičová

Karelin

et al. 2013

Scand J Immunol

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Several studies have established the potential efficacy of humoral immunity, primarily mannan-specific antibodies, in host protection against major fungal pathogen Candida albicans. In this study, we analysed humoral immune response induced by immunization with BSA-based conjugates bearing synthetic a-1, 6-branched oligomannosides (pentamannosides (M5) or hexamannosides (M6)) mimicking antigenic sequences of Candida cell wall mannan. We analysed the ability of antibodies prepared by immunization to recognize relevant antigenic determinants in mannan polysaccharide structure and in C. albicans yeast and hyphal morphoforms. M6-BSA conjugate induced markedly higher levels of mannan-specific IgG compared with M5-BSA conjugate. In contrast to M5-BSA conjugate, M6-BSA conjugate induced immunoglobulin isotype class switch from IgM to IgG, as revealed also from ELISPOT analysis. Immunizationinduced antibodies showed higher reactivity with hyphal form of C. albicans cells. The reduced immunogenicity of M5-BSA conjugate seems to be related to branching point location at terminal non-reducing end in comparison with M6-BSA oligomannoside with branching point at non-terminal location. Candidacidal activity assay revealed different capacity of sera prepared by immunization with M5-BSA and M6-BSA conjugates to improve candidacidal activity of polymorphonuclear leucocytes. Limited capacity of a-1,6-branched oligomannoside -BSA conjugates to induce antibodies significantly enhancing candidacidal activity of polymorphonuclear leucocytes -was presumably related to absence of antibodies with strong reactivity to corresponding antigenic determinants in natural cell wall mannan and with reduced ability to activate complement. The study documented markedly structure-dependent immunogenicity and limited capacity of branched a-mannooligosides conjugates to induce production of potentially protective antibodies.

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Section: Discussionsupporting

confidence: 80%

Effect of Branched α‐Oligomannoside Structures on Induction of Anti‐Candida Humoral Immune Response

Paulovičová

Karelin

et al. 2013

Scand J Immunol

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“…Zymosan, a crude particulate β-glucan obtained from cell walls of Saccharomyces cerevisiae is well known as a stimulator of the antibody-independent alternative pathway of complement activation (22–25). β-glucan from Candida albicans , a pathogenic fungus has also been shown to activate the alternative pathway of complement (26). Some studies have also shown a role for both the classical and the alternative pathways in opsonization of zymosan and glucan from the fungi Cryptococcus neoformans and Blastomyces dermatitidis (27–31).…”

Section: Introductionmentioning

confidence: 99%

Binding of Soluble Yeast β-Glucan to Human Neutrophils and Monocytes is Complement-Dependent

Bose¹,

Chan²,

Guerrero³

et al. 2013

Front. Immunol.

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The immunomodulatory properties of yeast β-1,3/1,6 glucans are mediated through their ability to be recognized by human innate immune cells. While several studies have investigated binding of opsonized and unopsonized particulate β-glucans to human immune cells mainly via complement receptor 3 (CR3) or Dectin-1, few have focused on understanding the binding characteristics of soluble β-glucans. Using a well-characterized, pharmaceutical-grade, soluble yeast β-glucan, this study evaluated and characterized the binding of soluble β-glucan to human neutrophils and monocytes. The results demonstrated that soluble β-glucan bound to both human neutrophils and monocytes in a concentration-dependent and receptor-specific manner. Antibodies blocking the CD11b and CD18 chains of CR3 significantly inhibited binding to both cell types, establishing CR3 as the key receptor recognizing the soluble β-glucan in these cells. Binding of soluble β-glucan to human neutrophils and monocytes required serum and was also dependent on incubation time and temperature, strongly suggesting that binding was complement-mediated. Indeed, binding was reduced in heat-inactivated serum, or in serum treated with methylamine or in serum reacted with the C3-specific inhibitor compstatin. Opsonization of soluble β-glucan was demonstrated by detection of iC3b, the complement opsonin on β-glucan-bound cells, as well as by the direct binding of iC3b to β-glucan in the absence of cells. Binding of β-glucan to cells was partially inhibited by blockade of the alternative pathway of complement, suggesting that the C3 activation amplification step mediated by this pathway also contributed to binding.

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“…Mannan is abundantly displayed on the cell surface of C. albicans, and it is resistant to complement activation (25). We have previously shown that the human antibody M1g1 can activate deposition of both mouse and human C3 on the cell surface of C. albicans (10,12).…”

Section: Discussionmentioning

confidence: 99%

“…Serum samples were stored at Ϫ80°C. For removal of naturally occurring antimannan antibodies (24,25), NMS was adsorbed two times with yeast cells, and NHS was adsorbed four times; each adsorption was performed with 5 ϫ 10 8 C. albicans 3153A yeast cells per ml of serum for 30 min at 0°C. The adsorbed serum was filtered and used immediately or stored at Ϫ80°C.…”

Section: Methodsmentioning

confidence: 99%

Influence of IgG Subclass on Human Antimannan Antibody-Mediated Resistance to Hematogenously Disseminated Candidiasis in Mice

et al. 2016

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bCandida albicans is a yeast-like pathogen and can cause life-threatening systemic candidiasis. Its cell surface is enriched with mannan that is resistant to complement activation. Previously, we developed the recombinant human IgG1 antimannan antibody M1g1. M1g1 was found to promote complement activation and phagocytosis and protect mice from systemic candidiasis. Here, we evaluate the influence of IgG subclass on antimannan antibody-mediated protection. Three IgG subclass variants of M1g1 were constructed: M1g2, M1g3, and M1g4. The IgG subclass identity for each variant was confirmed with DNA sequence and subclass-specific antibodies. These variants contain identical M1 Fabs and exhibited similar binding affinities for C. albicans yeast and purified mannan. Yeast cells and hyphae recovered from the kidney of antibody-treated mice with systemic candidiasis showed uniform binding of each variant, indicating constitutive expression of the M1 epitope and antibody opsonization in the kidney. All variants promoted deposition of both murine and human C3 onto the yeast cell surface, with M1g4 showing delayed activation, as determined by flow cytometry and immunofluorescence microscopy. M1g4-mediated complement activation was found to be associated with its M1 Fab that activates the alternative pathway in an Fc-independent manner. Treatment with each subclass variant extended the survival of mice with systemic candidiasis (P < 0.001). However, treatment with M1g1, M1g3, or M1g4, but not with M1g2, also reduced the kidney fungal burden (P < 0.001). Thus, the role of human antimannan antibody in host resistance to systemic candidiasis is influenced by its IgG subclass.

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Influence of Mannan and Glucan on Complement Activation and C3 Binding byCandida albicans

Cited by 26 publications

References 53 publications

Effect of Branched α‐Oligomannoside Structures on Induction of Anti‐Candida Humoral Immune Response

Effect of Branched α‐Oligomannoside Structures on Induction of Anti‐Candida Humoral Immune Response

Binding of Soluble Yeast β-Glucan to Human Neutrophils and Monocytes is Complement-Dependent

Influence of IgG Subclass on Human Antimannan Antibody-Mediated Resistance to Hematogenously Disseminated Candidiasis in Mice

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