Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier
Cryptococcus neoformans is a yeast responsible for disseminated meningoencephalitis in patients with cellular immune defects. The major virulence factor is the polysaccharide capsule. We took advantage of a relevant murine model of disseminated meningoencephalitis to study the early events associate...
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Veröffentlicht in: | The American journal of pathology 2005-02, Vol.166 (2), p.421-432 |
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description | Cryptococcus neoformans
is a yeast responsible for disseminated meningoencephalitis in patients with cellular immune defects. The major virulence factor is the polysaccharide capsule. We took advantage of a relevant murine model of disseminated meningoencephalitis to study the early events associated with blood-brain barrier (BBB) crossing. Mice were sacrificed at 1, 6, 24, and 48 hours post-intravenous inoculation, and classical histology, electron microscopy, and double immunofluorescence were used to study tissues and yeasts. Crossing of the BBB occurred early after inoculation, did not involve the choroid plexus but instead occurred at the level of the cortical capillaries, and caused early and severe damage to the structure of the microvessels. Seeding of the leptomeninges was not the primary event but occurred secondary to leakage of cortical pseudocysts. Organ invasion was associated with changes in cryptococcal capsule structure and cell size, which differed in terms of magnitude and kinetics, depending on both the organs involved, and potentially, on the bed structure of the local capillary. The rapid changes in capsule structure could contribute to inability of the host immune response to control cryptococcal infection in extrapulmonary spaces. |
doi_str_mv | 10.1016/S0002-9440(10)62265-1 |
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is a yeast responsible for disseminated meningoencephalitis in patients with cellular immune defects. The major virulence factor is the polysaccharide capsule. We took advantage of a relevant murine model of disseminated meningoencephalitis to study the early events associated with blood-brain barrier (BBB) crossing. Mice were sacrificed at 1, 6, 24, and 48 hours post-intravenous inoculation, and classical histology, electron microscopy, and double immunofluorescence were used to study tissues and yeasts. Crossing of the BBB occurred early after inoculation, did not involve the choroid plexus but instead occurred at the level of the cortical capillaries, and caused early and severe damage to the structure of the microvessels. Seeding of the leptomeninges was not the primary event but occurred secondary to leakage of cortical pseudocysts. Organ invasion was associated with changes in cryptococcal capsule structure and cell size, which differed in terms of magnitude and kinetics, depending on both the organs involved, and potentially, on the bed structure of the local capillary. The rapid changes in capsule structure could contribute to inability of the host immune response to control cryptococcal infection in extrapulmonary spaces.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>DOI: 10.1016/S0002-9440(10)62265-1</identifier><identifier>PMID: 15681826</identifier><identifier>CODEN: AJPAA4</identifier><language>eng</language><publisher>Bethesda, MD: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Blood-Brain Barrier ; Brain - microbiology ; Brain - pathology ; Collagen - chemistry ; Cryptococcus neoformans - metabolism ; Investigative techniques, diagnostic techniques (general aspects) ; Kinetics ; Male ; Medical sciences ; Meningitis, Cryptococcal - microbiology ; Meningitis, Cryptococcal - pathology ; Meningoencephalitis - microbiology ; Meningoencephalitis - pathology ; Mice ; Microcirculation - microbiology ; Microcirculation - pathology ; Microscopy, Electron ; Microscopy, Fluorescence ; Original Research Paper ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Phenotype ; Time Factors ; Tissue Distribution</subject><ispartof>The American journal of pathology, 2005-02, Vol.166 (2), p.421-432</ispartof><rights>2005 American Society for Investigative Pathology</rights><rights>2005 INIST-CNRS</rights><rights>Copyright © American Society for Investigative Pathology 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c578t-b9203e63146c45ab2adce01ae4aaf685ff995fce0e2720d2a8b1643d88745ece3</citedby><cites>FETCH-LOGICAL-c578t-b9203e63146c45ab2adce01ae4aaf685ff995fce0e2720d2a8b1643d88745ece3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1602336/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0002-9440(10)62265-1$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,3550,27924,27925,45995,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16565558$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15681826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Charlier, Caroline</creatorcontrib><creatorcontrib>Chrétien, Fabrice</creatorcontrib><creatorcontrib>Baudrimont, Marielle</creatorcontrib><creatorcontrib>Mordelet, Elodie</creatorcontrib><creatorcontrib>Lortholary, Olivier</creatorcontrib><creatorcontrib>Dromer, Françoise</creatorcontrib><title>Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><description>Cryptococcus neoformans
is a yeast responsible for disseminated meningoencephalitis in patients with cellular immune defects. The major virulence factor is the polysaccharide capsule. We took advantage of a relevant murine model of disseminated meningoencephalitis to study the early events associated with blood-brain barrier (BBB) crossing. Mice were sacrificed at 1, 6, 24, and 48 hours post-intravenous inoculation, and classical histology, electron microscopy, and double immunofluorescence were used to study tissues and yeasts. Crossing of the BBB occurred early after inoculation, did not involve the choroid plexus but instead occurred at the level of the cortical capillaries, and caused early and severe damage to the structure of the microvessels. Seeding of the leptomeninges was not the primary event but occurred secondary to leakage of cortical pseudocysts. Organ invasion was associated with changes in cryptococcal capsule structure and cell size, which differed in terms of magnitude and kinetics, depending on both the organs involved, and potentially, on the bed structure of the local capillary. The rapid changes in capsule structure could contribute to inability of the host immune response to control cryptococcal infection in extrapulmonary spaces.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood-Brain Barrier</subject><subject>Brain - microbiology</subject><subject>Brain - pathology</subject><subject>Collagen - chemistry</subject><subject>Cryptococcus neoformans - metabolism</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Kinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Meningitis, Cryptococcal - microbiology</subject><subject>Meningitis, Cryptococcal - pathology</subject><subject>Meningoencephalitis - microbiology</subject><subject>Meningoencephalitis - pathology</subject><subject>Mice</subject><subject>Microcirculation - microbiology</subject><subject>Microcirculation - pathology</subject><subject>Microscopy, Electron</subject><subject>Microscopy, Fluorescence</subject><subject>Original Research Paper</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Phenotype</subject><subject>Time Factors</subject><subject>Tissue Distribution</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS0EokvhI4B8AcEhYDuxk1xA3Yh_UiUOhbM160w2rpI42E6rfnuc7qoLJ06Wx7_3ZsaPkJecveeMqw9XjDGR1UXB3nL2TgmhZMYfkQ2XQmaC1_wx2TwgZ-RZCNfpqvKKPSVnXKqKV0JtCDYwh2VAehX9YuLikTY9THsM9CIEZyxEbOmtjT1t_N0cnXHGLIFO6DrnR5hCqrsQ7LSnrqOxR7odnGuzrQc70S14b9E_J086GAK-OJ7n5NeXzz-bb9nlj6_fm4vLzMiyitmuFixHlfNCmULCTkBrkHHAAqBTley6upZdKqEoBWsFVDuuirytqrKQaDA_Jx8PvvOyGzGJp-hh0LO3I_g77cDqf18m2-u9u9FcMZHnKhm8ORp493vBEPVog8FhgLTwErQq85qpukygPIBm3d5j99CEM70GpO8D0uvvr6X7gDRPuld_T3hSHRNJwOsjAMHA0HmYjA0nTkklpaxOk_Z2399ajzqMMAzJlmu4nrlSWuhCrB0_HUBMH3-TwtDBWJwMtklkom6d_c_MfwB9fby6</recordid><startdate>20050201</startdate><enddate>20050201</enddate><creator>Charlier, Caroline</creator><creator>Chrétien, Fabrice</creator><creator>Baudrimont, Marielle</creator><creator>Mordelet, Elodie</creator><creator>Lortholary, Olivier</creator><creator>Dromer, Françoise</creator><general>Elsevier Inc</general><general>ASIP</general><general>American Society for Investigative Pathology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20050201</creationdate><title>Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier</title><author>Charlier, Caroline ; Chrétien, Fabrice ; Baudrimont, Marielle ; Mordelet, Elodie ; Lortholary, Olivier ; Dromer, Françoise</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c578t-b9203e63146c45ab2adce01ae4aaf685ff995fce0e2720d2a8b1643d88745ece3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood-Brain Barrier</topic><topic>Brain - microbiology</topic><topic>Brain - pathology</topic><topic>Collagen - chemistry</topic><topic>Cryptococcus neoformans - metabolism</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Kinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Meningitis, Cryptococcal - microbiology</topic><topic>Meningitis, Cryptococcal - pathology</topic><topic>Meningoencephalitis - microbiology</topic><topic>Meningoencephalitis - pathology</topic><topic>Mice</topic><topic>Microcirculation - microbiology</topic><topic>Microcirculation - pathology</topic><topic>Microscopy, Electron</topic><topic>Microscopy, Fluorescence</topic><topic>Original Research Paper</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Phenotype</topic><topic>Time Factors</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Charlier, Caroline</creatorcontrib><creatorcontrib>Chrétien, Fabrice</creatorcontrib><creatorcontrib>Baudrimont, Marielle</creatorcontrib><creatorcontrib>Mordelet, Elodie</creatorcontrib><creatorcontrib>Lortholary, Olivier</creatorcontrib><creatorcontrib>Dromer, Françoise</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The American journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Charlier, Caroline</au><au>Chrétien, Fabrice</au><au>Baudrimont, Marielle</au><au>Mordelet, Elodie</au><au>Lortholary, Olivier</au><au>Dromer, Françoise</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier</atitle><jtitle>The American journal of pathology</jtitle><addtitle>Am J Pathol</addtitle><date>2005-02-01</date><risdate>2005</risdate><volume>166</volume><issue>2</issue><spage>421</spage><epage>432</epage><pages>421-432</pages><issn>0002-9440</issn><eissn>1525-2191</eissn><coden>AJPAA4</coden><abstract>Cryptococcus neoformans
is a yeast responsible for disseminated meningoencephalitis in patients with cellular immune defects. The major virulence factor is the polysaccharide capsule. We took advantage of a relevant murine model of disseminated meningoencephalitis to study the early events associated with blood-brain barrier (BBB) crossing. Mice were sacrificed at 1, 6, 24, and 48 hours post-intravenous inoculation, and classical histology, electron microscopy, and double immunofluorescence were used to study tissues and yeasts. Crossing of the BBB occurred early after inoculation, did not involve the choroid plexus but instead occurred at the level of the cortical capillaries, and caused early and severe damage to the structure of the microvessels. Seeding of the leptomeninges was not the primary event but occurred secondary to leakage of cortical pseudocysts. Organ invasion was associated with changes in cryptococcal capsule structure and cell size, which differed in terms of magnitude and kinetics, depending on both the organs involved, and potentially, on the bed structure of the local capillary. The rapid changes in capsule structure could contribute to inability of the host immune response to control cryptococcal infection in extrapulmonary spaces.</abstract><cop>Bethesda, MD</cop><pub>Elsevier Inc</pub><pmid>15681826</pmid><doi>10.1016/S0002-9440(10)62265-1</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biological and medical sciences Blood-Brain Barrier Brain - microbiology Brain - pathology Collagen - chemistry Cryptococcus neoformans - metabolism Investigative techniques, diagnostic techniques (general aspects) Kinetics Male Medical sciences Meningitis, Cryptococcal - microbiology Meningitis, Cryptococcal - pathology Meningoencephalitis - microbiology Meningoencephalitis - pathology Mice Microcirculation - microbiology Microcirculation - pathology Microscopy, Electron Microscopy, Fluorescence Original Research Paper Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Phenotype Time Factors Tissue Distribution |
title | Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier |
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