In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 5 ( 2009-02-03), p. 1506-1511
Kurzfassung:
The 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, Spα, 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 β-glucan but not by mannan. The K d of the rshCD5/(1→3)-β- 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)-β- d -glucans] and support the therapeutic potential of soluble CD5 forms in fungal sepsis.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0805846106
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
2009
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12
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