Role of Mannoprotein in Induction and Regulation of Immunity to<i>Cryptococcus neoformans</i>

Pietrella, Donatella; Cherniak, Robert; Strappini, Carla; Perito, Stefano; Mosci, Paolo; Bistoni, Francesco; Vecchiarelli, Anna

doi:10.1128/iai.69.5.2808-2814.2001

Cited by 65 publications

(47 citation statements)

References 37 publications

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“…More recently the molecular characterization of a C. neoformans MP that stimulates a T-cell response has been provided (13,14). We have shown that our MP preparation from C. neoformans is capable of inducing IL-12 production from human monocytes and protection against a lethal fungus challenge (21,22). Thus, MPs from C. albicans and C. neoformans appear to play an important role in the elicitation of protective antifungal responses.…”

Section: Discussionmentioning

confidence: 83%

“…Furthermore, in vivo treatment with MP induces IL-12 secretion by splenic macrophages and IL-12 p40 mRNA expression in the brain. MP-induced IL-12 and IFN-␥ secretion coincides with enhanced antifungal activity, resolution of the inflammatory process, and clearance of fungal load from the brain (21).…”

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confidence: 82%

“…In particular, Candida and Cryptococcus MPs were shown elsewhere to induce lymphoproliferation (19,23) and cytokine production (21,22,27). Previous data showed that interleukin-12 (IL-12) plays a pivotal role in induction of the Thelper type 1 (Th1) response against C. neoformans infection, this response being essential for protection (6).…”

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confidence: 99%

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Mannoprotein fromCryptococcus neoformansPromotes T-Helper Type 1 Anticandidal Responses in Mice

et al. 2002

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We previously demonstrated that mannoprotein (MP) from Cryptococcus neoformans (CnMP) stimulates interleukin-12 production by human monocytes, thus fostering a T-helper type 1 (Th1) protective anticryptococcal response. In this paper we show that CnMP was also able to induce a Candida albicans-directed protective Th1 response. This was demonstrated for mice immunized with CnMP by induction of a delayed-type hypersensitivity (DTH) reaction to C. albicans MP (CaMP) as well as induction of gamma interferon production by CD4؉ and CD8 ؉ splenic T cells stimulated in vitro with CaMP. CnMP-immunized mice were also partially protected from lethal systemic challenge with C. albicans, as shown by prolonged median survival times and decreased fungal burden in the kidney. Much evidence supports the validity of these cross-reactive and functional Th1 responses: (i) a non-cross-reactive C. albicans antigen, such as enolase, did not produce a DTH response to CaMP; (ii) passive adoptive transfer of T cells primed with CnMP induced a DTH reaction; (iii) C. neoformans extract elicited a DTH response to CaMP; and (iv) a monoclonal antibody (7H6) directed against a major and immunodominant T-cell-stimulatory 65-kDa MP (MP65) of C. albicans also recognized discrete 100-kDa constituents of C. neoformans extracts, as well as secretory constituents of the fungus. These results suggest the presence of common Th1 antigenic determinants in the mannoproteic material of C. neoformans and C. albicans epitopes, which should be considered in devising common strategies for immunoprophylactic or immunotherapeutic control of the fungi.

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Section: Discussionmentioning

confidence: 83%

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confidence: 82%

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Mannoprotein fromCryptococcus neoformansPromotes T-Helper Type 1 Anticandidal Responses in Mice

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“…If denture plaque reacts similarly to dental plaque, it is likely that sugar will cause the production of acid. Mannoproteins that are present on the surface of C albicans may possess immunomodulatory properties (63), and these molecules, along with other biofilm exopolymers, may induce inflammation.…”

Section: Oral Biofilms Under the Influence Of Selection Forcesmentioning

confidence: 99%

The Buccale Puzzle: The Symbiotic Nature of Endogenous Infections of the Oral Cavity

Ruby

Barbeau

2002

Canadian Journal of Infectious Diseases and Medical Microbiolog

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“…When monocytes were cocultured with autologous T cells, an intense proliferation of T cells with production of gamma interferon (IFN-␥) was observed (36,37). The possibility that this type of immune response could be elicited in vivo after administration of MPs was corroborated in an experimental mouse model of systemic cryptococcosis (33). MP treatment conferred protection against C. neoformans lethal challenge by concomitant induction of a Th1-type response characterized by an early and massive presence of IL-12 (33).…”

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confidence: 98%

Mannoproteins fromCryptococcus neoformansPromote Dendritic Cell Maturation and Activation

et al. 2005

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Our previous data show that mannoproteins (MPs) from Cryptococcus neoformans are able to induce protective responses against both C. neoformans and Candida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to IB␣ phosphorylation, which is necessary for nuclear factor B transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi.

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Role of Mannoprotein in Induction and Regulation of Immunity toCryptococcus neoformans

Cited by 65 publications

References 37 publications

Mannoprotein fromCryptococcus neoformansPromotes T-Helper Type 1 Anticandidal Responses in Mice

Mannoprotein fromCryptococcus neoformansPromotes T-Helper Type 1 Anticandidal Responses in Mice

The Buccale Puzzle: The Symbiotic Nature of Endogenous Infections of the Oral Cavity

Mannoproteins fromCryptococcus neoformansPromote Dendritic Cell Maturation and Activation

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