Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection.
Cryptococcal meningoencephalitis is the most common fungal disease in the central nervous system. The mechanisms by which Cryptococcus neoformans invades the brain are largely unknown. In this study, we found that C. neoformans-derived microvesicles (CnMVs) can enhance the traversal of the blood-bra...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3492498?pdf=render |
| _version_ | 1818976108449628160 |
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| author | Sheng-He Huang Chun-Hua Wu Yun C Chang Kyung J Kwon-Chung Robert J Brown Ambrose Jong |
| author_facet | Sheng-He Huang Chun-Hua Wu Yun C Chang Kyung J Kwon-Chung Robert J Brown Ambrose Jong |
| author_sort | Sheng-He Huang |
| collection | DOAJ |
| description | Cryptococcal meningoencephalitis is the most common fungal disease in the central nervous system. The mechanisms by which Cryptococcus neoformans invades the brain are largely unknown. In this study, we found that C. neoformans-derived microvesicles (CnMVs) can enhance the traversal of the blood-brain barrier (BBB) by C. neoformans invitro. The immunofluorescence imaging demonstrates that CnMVs can fuse with human brain microvascular endothelial cells (HBMECs), the constituents of the BBB. This activity is presumably due to the ability of the CnMVs to activate HBMEC membrane rafts and induce cell fusogenic activity. CnMVs also enhanced C. neoformans infection of the brain, found in both infected brains and cerebrospinal fluid. In infected mouse brains, CnMVs are distributed inside and around C. neoformans-induced cystic lesions. GFAP (glial fibrillary acidic protein)-positive astrocytes were found surrounding the cystic lesions, overlapping with the 14-3-3-GFP (14-3-3-green fluorescence protein fusion) signals. Substantial changes could be observed in areas that have a high density of CnMV staining. This is the first demonstration that C. neoformans-derived microvesicles can facilitate cryptococcal traversal across the BBB and accumulate at lesion sites of C. neoformans-infected brains. Results of this study suggested that CnMVs play an important role in the pathogenesis of cryptococcal meningoencephalitis. |
| first_indexed | 2024-12-20T16:06:36Z |
| format | Article |
| id | doaj.art-046bca93ba674674a0489d85973ba913 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T16:06:36Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-046bca93ba674674a0489d85973ba9132022-12-21T19:34:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4857010.1371/journal.pone.0048570Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection.Sheng-He HuangChun-Hua WuYun C ChangKyung J Kwon-ChungRobert J BrownAmbrose JongCryptococcal meningoencephalitis is the most common fungal disease in the central nervous system. The mechanisms by which Cryptococcus neoformans invades the brain are largely unknown. In this study, we found that C. neoformans-derived microvesicles (CnMVs) can enhance the traversal of the blood-brain barrier (BBB) by C. neoformans invitro. The immunofluorescence imaging demonstrates that CnMVs can fuse with human brain microvascular endothelial cells (HBMECs), the constituents of the BBB. This activity is presumably due to the ability of the CnMVs to activate HBMEC membrane rafts and induce cell fusogenic activity. CnMVs also enhanced C. neoformans infection of the brain, found in both infected brains and cerebrospinal fluid. In infected mouse brains, CnMVs are distributed inside and around C. neoformans-induced cystic lesions. GFAP (glial fibrillary acidic protein)-positive astrocytes were found surrounding the cystic lesions, overlapping with the 14-3-3-GFP (14-3-3-green fluorescence protein fusion) signals. Substantial changes could be observed in areas that have a high density of CnMV staining. This is the first demonstration that C. neoformans-derived microvesicles can facilitate cryptococcal traversal across the BBB and accumulate at lesion sites of C. neoformans-infected brains. Results of this study suggested that CnMVs play an important role in the pathogenesis of cryptococcal meningoencephalitis.http://europepmc.org/articles/PMC3492498?pdf=render |
| spellingShingle | Sheng-He Huang Chun-Hua Wu Yun C Chang Kyung J Kwon-Chung Robert J Brown Ambrose Jong Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection. PLoS ONE |
| title | Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection. |
| title_full | Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection. |
| title_fullStr | Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection. |
| title_full_unstemmed | Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection. |
| title_short | Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection. |
| title_sort | cryptococcus neoformans derived microvesicles enhance the pathogenesis of fungal brain infection |
| url | http://europepmc.org/articles/PMC3492498?pdf=render |
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