Effects of altered N-glycan structures of Cryptococcus neoformans mannoproteins, MP98 (Cda2) and MP84 (Cda3), on interaction with host cells
Abstract Cryptococcus neoformans is an opportunistic human fungal pathogen causing lethal meningoencephalitis. It has several cell wall mannoproteins (MPs) identified as immunoreactive antigens. To investigate the structure and function of N-glycans assembled on cryptococcal cell wall MPs in host ce...
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| Format: | Article |
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Nature Portfolio
2023-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-27422-9 |
| _version_ | 1797945884269346816 |
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| author | Su-Bin Lee Catia Mota Eun Jung Thak Jungho Kim Ye Ji Son Doo-Byoung Oh Hyun Ah Kang |
| author_facet | Su-Bin Lee Catia Mota Eun Jung Thak Jungho Kim Ye Ji Son Doo-Byoung Oh Hyun Ah Kang |
| author_sort | Su-Bin Lee |
| collection | DOAJ |
| description | Abstract Cryptococcus neoformans is an opportunistic human fungal pathogen causing lethal meningoencephalitis. It has several cell wall mannoproteins (MPs) identified as immunoreactive antigens. To investigate the structure and function of N-glycans assembled on cryptococcal cell wall MPs in host cell interactions, we purified MP98 (Cda2) and MP84 (Cda3) expressed in wild-type (WT) and N-glycosylation-defective alg3 mutant (alg3Δ) strains. HPLC and MALDI-TOF analysis of the MP proteins from the WT revealed protein-specific glycan structures with different extents of hypermannosylation and xylose/xylose phosphate addition. In alg3Δ, MP98 and MP84 had truncated core N-glycans, containing mostly five and seven mannoses (M5 and M7 forms), respectively. In vitro adhesion and uptake assays indicated that the altered core N-glycans did not affect adhesion affinities to host cells although the capacity to induce the immune response of bone-marrow derived dendritic cells (BMDCs) decreased. Intriguingly, the removal of all N-glycosylation sites on MP84 increased adhesion to host cells and enhanced the induction of cytokine secretion from BMDCs compared with that on MP84 carrying WT N-glycans. Therefore, the structure-dependent effects of N-glycans suggested their complex roles in modulating the interaction of MPs with host cells to avoid nonspecific adherence to host cells and host immune response hyperactivation. |
| first_indexed | 2024-04-10T21:03:16Z |
| format | Article |
| id | doaj.art-7ecc353392474abab855bc11e6126668 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T21:03:16Z |
| publishDate | 2023-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7ecc353392474abab855bc11e61266682023-01-22T12:13:02ZengNature PortfolioScientific Reports2045-23222023-01-0113111410.1038/s41598-023-27422-9Effects of altered N-glycan structures of Cryptococcus neoformans mannoproteins, MP98 (Cda2) and MP84 (Cda3), on interaction with host cellsSu-Bin Lee0Catia Mota1Eun Jung Thak2Jungho Kim3Ye Ji Son4Doo-Byoung Oh5Hyun Ah Kang6Department of Life Science, College of Natural Science, Chung-Ang UniversityDepartment of Life Science, College of Natural Science, Chung-Ang UniversityDepartment of Life Science, College of Natural Science, Chung-Ang UniversityDepartment of Life Science, College of Natural Science, Chung-Ang UniversityDepartment of Life Science, College of Natural Science, Chung-Ang UniversityKorea Research Institute of Bioscience and Biotechnology (KRIBB)Department of Life Science, College of Natural Science, Chung-Ang UniversityAbstract Cryptococcus neoformans is an opportunistic human fungal pathogen causing lethal meningoencephalitis. It has several cell wall mannoproteins (MPs) identified as immunoreactive antigens. To investigate the structure and function of N-glycans assembled on cryptococcal cell wall MPs in host cell interactions, we purified MP98 (Cda2) and MP84 (Cda3) expressed in wild-type (WT) and N-glycosylation-defective alg3 mutant (alg3Δ) strains. HPLC and MALDI-TOF analysis of the MP proteins from the WT revealed protein-specific glycan structures with different extents of hypermannosylation and xylose/xylose phosphate addition. In alg3Δ, MP98 and MP84 had truncated core N-glycans, containing mostly five and seven mannoses (M5 and M7 forms), respectively. In vitro adhesion and uptake assays indicated that the altered core N-glycans did not affect adhesion affinities to host cells although the capacity to induce the immune response of bone-marrow derived dendritic cells (BMDCs) decreased. Intriguingly, the removal of all N-glycosylation sites on MP84 increased adhesion to host cells and enhanced the induction of cytokine secretion from BMDCs compared with that on MP84 carrying WT N-glycans. Therefore, the structure-dependent effects of N-glycans suggested their complex roles in modulating the interaction of MPs with host cells to avoid nonspecific adherence to host cells and host immune response hyperactivation.https://doi.org/10.1038/s41598-023-27422-9 |
| spellingShingle | Su-Bin Lee Catia Mota Eun Jung Thak Jungho Kim Ye Ji Son Doo-Byoung Oh Hyun Ah Kang Effects of altered N-glycan structures of Cryptococcus neoformans mannoproteins, MP98 (Cda2) and MP84 (Cda3), on interaction with host cells Scientific Reports |
| title | Effects of altered N-glycan structures of Cryptococcus neoformans mannoproteins, MP98 (Cda2) and MP84 (Cda3), on interaction with host cells |
| title_full | Effects of altered N-glycan structures of Cryptococcus neoformans mannoproteins, MP98 (Cda2) and MP84 (Cda3), on interaction with host cells |
| title_fullStr | Effects of altered N-glycan structures of Cryptococcus neoformans mannoproteins, MP98 (Cda2) and MP84 (Cda3), on interaction with host cells |
| title_full_unstemmed | Effects of altered N-glycan structures of Cryptococcus neoformans mannoproteins, MP98 (Cda2) and MP84 (Cda3), on interaction with host cells |
| title_short | Effects of altered N-glycan structures of Cryptococcus neoformans mannoproteins, MP98 (Cda2) and MP84 (Cda3), on interaction with host cells |
| title_sort | effects of altered n glycan structures of cryptococcus neoformans mannoproteins mp98 cda2 and mp84 cda3 on interaction with host cells |
| url | https://doi.org/10.1038/s41598-023-27422-9 |
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