Heat-Shock Mannoproteins as Targets of Secretory IgA in Candida albicans

Polonelli, Luciano; Gerloni, Mara; Conti, Stefania; Fisicaro, Paola; Cantelli, C.; Portincasa, P.; Almondo, F.; Barea, Pedro; Hernando, Fernando; Pontón, José

doi:10.1093/infdis/169.6.1401

Cited by 26 publications

(27 citation statements)

References 13 publications

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“…This reactivity was expected, since the mice from whom the splenocytes were obtained were immunized with one of the cell wall stress mannoproteins that have been found to be major targets for salivary sIgA (29). Heat shock proteins are highly conserved and have been shown to be among the dominant antigens recognized in immune responses to a broad spectrum of pathogens (41), including C. albicans and other fungi (22).…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, we have demonstrated that salivary sIgA reacts with a group of stress mannoproteins located on the cell wall surface-mannoproteins whose expression is modulated by a number of factors, including the temperature of growth, composition of growth medium, yeast-mycelium transition, and pH (3,29,31,39). We have also demonstrated that salivary sIgA inhibits the adhesion of C. albicans to plastic and composite restorative dental materials and that the inhibitory effect can be mimicked by MAbs directed against cell wall antigens of C. albicans (24,36).…”

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confidence: 99%

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A Monoclonal Antibody Directed against aCandida albicansCell Wall Mannoprotein Exerts Three Anti-C. albicansActivities

Moragues¹,

Omaetxebarria²,

Elguezabal³

et al. 2003

Infect Immun

152

128

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Antibodies are believed to play a role in the protection against Candida albicans infections by a number of mechanisms, including the inhibition of adhesion or germ tube formation, opsonization, neutralization of virulence-related enzymes, and direct candidacidal activity. Although some of these biological activities have been demonstrated individually in monoclonal antibodies (MAbs), it is not clear if all these anti-C. albicans activities can be displayed by a single antibody. In this report, we characterized a monoclonal antibody raised against the main target of salivary secretory immunoglobulin A in the cell wall of C. albicans, which exerts three anti-C. albicans activities: (i) inhibition of adherence to HEp-2 cells, (ii) inhibition of germination, and (iii) direct candidacidal activity. MAb C7 reacted with a proteinic epitope from a mannoprotein with a molecular mass of >200 kDa predominantly expressed on the C. albicans germ tube cell wall surface as well as with a number of antigens from Candida lusitaniae, Cryptococcus neoformans, Aspergillus fumigatus, and Scedosporium prolificans. MAb C7 caused a 31.1% inhibition in the adhesion of C. albicans to HEp-2 monolayers and a 55.3% inhibition in the adhesion of C. albicans to buccal epithelial cells, produced a 38.5% decrease in the filamentation of C. albicans, and exhibited a potent fungicidal effect against C. albicans, C. lusitaniae, Cryptococcus neoformans, A. fumigatus, and S. prolificans, showing reductions in fungal growth ranging from 34.2 to 88.7%. The fungicidal activity showed by MAb C7 seems to be related to that reported by antibodies mimicking the activity of a killer toxin produced by the yeast Pichia anomala, since one of these MAbs also reacted with the C. albicans mannoprotein with a molecular mass of >200 kDa. Results presented in this study support the concept of a family of microbicidal antibodies that could be useful in the treatment of a wide range of microbial infections when used alone or in combination with current antimicrobial agents.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A Monoclonal Antibody Directed against aCandida albicansCell Wall Mannoprotein Exerts Three Anti-C. albicansActivities

Moragues¹,

Omaetxebarria²,

Elguezabal³

et al. 2003

Infect Immun

152

128

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“…They were produced following standard methods in BALB/c mice immunized by subcutaneous injections of a partly purified antigen of 260 kDa from germ tubes (PA lOF) and a partly purified heat shock mannoprotein of 200 kDa from a blastoconidium extract (C6) as previously described (Ponton et al, 1993;Polonelli et al, 1994). Antibodies used in this study were contained in ascites fluid from mice injected with the hybridomas.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

“…Our group has been working during the past few years on the development of monoclonal antibodies against C. albicans antigenic determinants, also including C. albicans heat shock mannoproteins (Ponton et al, 1993;Polonelli et al, 1994). We have tested a panel of these antibodies on human ovarian carcinoma tissue, and two of them showed promising initial results in a small preliminary study.…”

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confidence: 99%

Cross-reactivity between Candida albicans and human ovarian carcinoma as revealed by monoclonal antibodies PA10F and C6

Schneider

Moragues²,

Martínez³

et al. 1998

Br J Cancer

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Summary Antibodies against Candida albicans antigenic determinants have been reported to cross-react with human tumour cells. We have found that two monoclonal antibodies, C6 and PAl OF, developed at our laboratory against C. albicans antigenic determinants, cross-react with human ovarian cancer on Western blots and immunohistochemistry. We have subsequently used one of them, PA1OF, to test by means of immunohistochemistry a series of 37 human ovarian carcinomas. Out of 37 tumours, 25 (67.6%) expressed the antigen recognized by PAl OF. The reactivity, however, was concentrated on the subgroup of particularly aggressive, invasive carcinomas in advanced stages of the disease (19 out of 24 positive), whereas the antigen was expressed significantly less (P = 0.0007) in the subgroup of much less aggressive stage I tumours of low malignant potential, also called borderline carcinomas (2 out of 13 positive). This cross-reactivity between C. albicans and ovarian carcinoma seems to be attributable to a common antigenic determinant related to tumour aggressiveness.

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“…Monoclonal antibody (MAb) C7 was raised against a protein epitope of a stress mannoprotein of Ͼ200 kDa that is the main target of salivary secretory immunoglobulin A (IgA) in the cell wall of Candida albicans (7). This MAb exhibits potent fungicidal activity against C. albicans, Candida lusitaniae, Cryptococcus neoformans, Aspergillus fumigatus, and Scedosporium prolificans (5), and it has been shown to protect mice from invasive candidiasis (10).…”

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confidence: 99%