The CD5 ectodomain interacts with conserved fungal cell wall components and protects from zymosan-induced septic shock-like syndrome

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dc.contributor.authorVera, Jorge
dc.contributor.authorFenutría, Rafael
dc.contributor.authorCañadas Benito, Olga
dc.contributor.authorFigueras, Maite
dc.contributor.authorMota, Rubén
dc.contributor.authorSarrias, Maria Rosa
dc.contributor.authorWilliams, David L.
dc.contributor.authorCasals Carro, María Cristina
dc.contributor.authorYelamos, José
dc.contributor.authorLozano, Francisco
dc.date.accessioned2024-01-15T19:04:00Z
dc.date.available2024-01-15T19:04:00Z
dc.date.issued2009-02-03
dc.description.abstractThe CD5 lymphocyte surface receptor is a group B member of the ancient and highly conserved scavenger receptor cysteine-rich superfamily. CD5 is expressed on mature T and B1a cells, where it is known to modulate lymphocyte activation and/or differentiation processes. Recently, the interaction of a few group B SRCR members (CD6, Spalpha, and DMBT1) with conserved microbial structures has been reported. Protein binding assays presented herein indicate that the CD5 ectodomain binds to and aggregates fungal cells (Schizosaccharomyces pombe, Candida albicans, and Cryptococcus neoformans) but not to Gram-negative (Escherichia coli) or Gram-positive (Staphylococcus aureus) bacteria. Accordingly, the CD5 ectodomain binds to zymosan but not to purified bacterial cell wall constituents (LPS, lipotheicoic acid, or peptidoglycan), and such binding is specifically competed by beta-glucan but not by mannan. The K(d) of the rshCD5/(1-->3)-beta-d-glucan phosphate interaction is 3.7 +/- 0.2 nM as calculated from tryptophan fluorescence data analysis of free and bound rshCD5. Moreover, zymosan binds to membrane-bound CD5, and this induces both MAPK activation and cytokine release. In vivo validation of the fungal binding properties of the CD5 ectodomain is deduced from its protective effect in a mouse model of zymosan-induced septic shock-like syndrome. In conclusion, the present results indicate that the CD5 lymphocyte receptor may sense the presence of conserved fungal components [namely, (1-->3)-beta-d-glucans] and support the therapeutic potential of soluble CD5 forms in fungal sepsis.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Educación
dc.description.sponsorshipRed Española de Investigación en Patología Infecciosa
dc.description.sponsorshipFondo de Investigación Sanitaria
dc.description.sponsorshipNational Institutes of Health (NIH)
dc.description.statuspub
dc.identifier.citationVera J, Fenutría R, Cañadas O, Figueras M, Mota R, Sarrias MR, Williams DL, Casals C, Yelamos J, Lozano F. The CD5 ectodomain interacts with conserved fungal cell wall components and protects from zymosan-induced septic shock-like syndrome. Proc. Natl. Acad. Sci. USA. 2009 Feb 3; 106(5): 1506-1511
dc.identifier.doi10.1073/pnas.0805846106
dc.identifier.issn0027-8424
dc.identifier.officialurlhttps://www.pnas.org/doi/10.1073/pnas.0805846106
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93225
dc.issue.number5
dc.journal.titlePNAS (Proceedings of the National Academy of Sciences)
dc.language.isoeng
dc.page.final1511
dc.page.initial1506
dc.publisherNational Academy of Science
dc.relation.projectID(SAF2004–3251, SAF 2007–62197, SAF2006–04434)
dc.relation.projectID(RD06/0008/1013)
dc.relation.projectID(GM53522)
dc.relation.projectID(CP05/100)
dc.rights.accessRightsrestricted access
dc.subject.cdu577.112
dc.subject.cdu612.017
dc.subject.keywordβ-glucans
dc.subject.keywordFungal sepsis
dc.subject.keywordLymphocytes
dc.subject.keywordScavenger receptor
dc.subject.ucmBioquímica (Biología)
dc.subject.ucmInmunología
dc.subject.unesco2302 Bioquímica
dc.subject.unesco2412 Inmunología
dc.titleThe CD5 ectodomain interacts with conserved fungal cell wall components and protects from zymosan-induced septic shock-like syndrome
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number106
dspace.entity.typePublication
relation.isAuthorOfPublication25a89a2f-a381-4f15-9a6b-59430ee96a63
relation.isAuthorOfPublicationd4e23d80-fa5c-4614-bd2d-2c391b596713
relation.isAuthorOfPublication.latestForDiscovery25a89a2f-a381-4f15-9a6b-59430ee96a63
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