Separation of immunomodulatory effects of mannan from Candida albicans into stimulatory and suppressive components

Domer, Judith E.; Stashak, Philip W.; Elkins, Karen L.; Prescott, Benjamin; Caldes, George; Baker, Phillip J.

doi:10.1016/0008-8749(86)90153-x

Cited by 45 publications

(21 citation statements)

References 43 publications

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“…The 14 kinds of structurally different branches described for mannan isolated from C. albicans J-1012 (81) illustrate the possibilities for variation among mannan molecules from a single source. The heterogeneity of mannan observed in terms of size by electrophoresis (44) and in terms of charge by ion-exchange chromatography (35) also illustrate this principle. Mannan must therefore be thought of as a family of glycoproteins structured on a common theme, as a heterogeneous mixture of polymers of varying sizes and compositions.…”

Section: Chemistry Of Mannanmentioning

confidence: 82%

“…While isolation of individual mannan species is essentially impossible, mannan can be further fractionated by ionexchange chromatography (35). This procedure has been used to provide five charge classes of mannan but, because the salt gradient used to elute the column is discontinuous, even these mannan fractions cannot be considered homogeneous.…”

Section: Methods Of Mannan Preparationmentioning

confidence: 99%

“…This finding, together with another by Koster et al (87), suggests that lymphocytes can also become sensitized to PGE2 in vivo by conditions that affect the number and/or affinity of membrane receptors for this agonist. Koster (35) have also reported that suppressor cells are generated in response to C. albicans polysaccharide or components of bulk mannan, but the mechanism(s) involved in these phenomena was not further defined. From other studies unrelated to candidiasis, it becomes possible to speculate about additional characteristics of a suppressor lymphocyte-monocyte circuit in patients with CMC.…”

Section: Studies Identifying Mannan As An Immunoinhibitor In Cmcmentioning

confidence: 99%

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Candida mannan: chemistry, suppression of cell-mediated immunity, and possible mechanisms of action

et al. 1991

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The ability of Candida albicans to establish an infection involves multiple components of this fungal pathogen, but its ability to persist in host tissue may involve primarily the immunosuppressive property of a major cell wall glycoprotein, mannan. Mannan and oligosaccharide fragments of mannan are potent inhibitors of cell-mediated immunity and appear to reproduce the immune deficit of patients with the mucocutaneous form of candidiasis. However, neither the exact structures of these inhibitory species nor their mechanisms of action have yet been clearly defined. Different investigators have proposed that mannan or mannan catabolites act upon monocytes or suppressor T lymphocytes, but research from unrelated areas has provided still other possibilities for consideration. These include interference with cytokine activities, lymphocyte-monocyte interactions, and leukocyte homing. To stimulate further research of the immunosuppressive property of C. albicans mannan, we have reviewed (i) the relationship of mannan to other antigens and virulence factors of the fungus; (ii) the chemistry of mannan, together with methods for preparation of mannan and mannan fragments; and (iii) the historical evidence for immunosuppression by Candida mannan and the mechanisms currently proposed for this property; and (iv) we have speculated upon still other mechanisms by which mannan might influence host defense functions. It is possible that understanding the immunosuppressive effects of mannan will provide clues to novel therapies for candidiasis that will enhance the efficacy of both available and future anti-Candida agents.

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Section: Chemistry Of Mannanmentioning

confidence: 82%

Section: Methods Of Mannan Preparationmentioning

confidence: 99%

Section: Studies Identifying Mannan As An Immunoinhibitor In Cmcmentioning

confidence: 99%

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Candida mannan: chemistry, suppression of cell-mediated immunity, and possible mechanisms of action

et al. 1991

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“…Many other immunomodulatory effects, including the induction of immunosuppressive activities against both B and T cell-mediated responses, have been also ascribed to mannoproteins or 'mannan' of C. albicans (Carrow & Domer, 1985 Podzorski et al, 1989Podzorski et al, , 1990. In view of the complexity of the biological response 0001-6149 O 1990 SGM modifier properties expressed by candidal mannoproteins, including both immunoenhancing and immunosuppressive effects (Domer et al, 1986(Domer et al, , 1987, it is important to examine distinct mannoprotein fractions separately for their immunological effects. This paper focuses on chromatographically separated, chemically and antigenically defined mannoprotein fractions that are responsible for the overall immunoenhancing activity of the crude mannoprotein extract of C. albicans.…”

Section: Introductionmentioning

confidence: 99%

Lymphoproliferative and cytotoxic responses of human peripheral blood mononuclear cells to mannoprotein constituents of Candida albicans

Torosantucci

Palma²,

Boccanera³

et al. 1990

Journal of General Microbiology

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Two major proteoglycan constituents (designated F1 and F2) of the cell wall of Candida albicans were separated by ion-exchange chromatography from a crude carbohydrate-rich extract (GMP), and investigated for their chemical and molecular composition, antigenicity and immunomodulatory properties in cultures of human peripheral blood mononuclear cells (PBMC). Both fractions consisted predominantly of Periodic acidSchitf (PAS) and concanavalin A (Con A)-reactive material consisting of > 90 % mannose, 3-5% protein and small amounts of phosphorus; each was recognized by an anti-Candida rabbit serum as well as by a monoclonal antibody (mAb AF1) directed against an oligosaccharide epitope present on the fungal cell surface. When F1 and F2 were subjected to SDS-PAGE, transblotted and stained with enzyme-conjugated mAb AF1 or Con A, most of the antibody or lectin bound to high molecular mass (> 200 kDa) polydisperse material, some of which was present in F2 (as in the starting GMP extract) but absent in F1. This difference was also observed in PAS-stained gels of the two fractions.The F2, but not the F1, constituent was as active as the unfractionated GMP extract in inducing lymphoproliferation, production of the cytokines interleukin-2 and interferon-y, and generation of cytotoxicity against a natural-killer-sensitive target cell line (K562). These immunomodulatory properties were, like those possessed by GMP, protease-sensitive and heat-stable. Treatment of PBMC cultures with a modulatory anti-Tcell receptor antibody abolished the lymphoproliferation induced by GMP and F2 but not that induced by phytohaemagglutinin, showing that the mannoprotein materials of C. albicans acted through interaction with the antigen receptor complex.

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“…have been obtained and used for diagnostic (Miyakawa et al, 1986) or physiological Cutler, 1984, 1986;Hopwood et al, 1986) studies, these reagents were not produced by immunisation with a soluble glucomannoprotein extract. The low intrinsic antimannoprotein humoral immune response in mice has been observed repeatedly, and Domer et al (1986) have demonstrated that some mannoprotein from the cell wall of C. albicans may suppress the B-lymphocyte response. A MAB has been obtained by immunisation with a previously characterised glucomannoprotein-rich antigenic extract (GMP) from the cell wall of C. albicans (Ausiello et al, 1986;Scaringi et al, 1988).…”

Section: Introductionmentioning

confidence: 89%

Production and characterisation of a monoclonal antibody to a cell-surface, glucomannoprotein constituent of Candida albicans and other pathogenic Candida species

Cassone

Torosantucci

Boccanera

et al. 1988

Journal of Medical Microbiology

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Separation of immunomodulatory effects of mannan from Candida albicans into stimulatory and suppressive components

Cited by 45 publications

References 43 publications

Candida mannan: chemistry, suppression of cell-mediated immunity, and possible mechanisms of action

Candida mannan: chemistry, suppression of cell-mediated immunity, and possible mechanisms of action

Lymphoproliferative and cytotoxic responses of human peripheral blood mononuclear cells to mannoprotein constituents of Candida albicans

Production and characterisation of a monoclonal antibody to a cell-surface, glucomannoprotein constituent of Candida albicans and other pathogenic Candida species

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