CD44 as a receptor for colonization of the pharynx by group A Streptococcus
Colette Cywes, … , Ivan Stamenkovic, Michael R. Wessels
Colette Cywes, … , Ivan Stamenkovic, Michael R. Wessels
Published October 15, 2000
Citation Information: J Clin Invest. 2000;106(8):995-1002. https://doi.org/10.1172/JCI10195.
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Article

CD44 as a receptor for colonization of the pharynx by group A Streptococcus

Abstract

The pharynx is the primary reservoir for strains of group A Streptococcus (GAS) associated both with pharyngitis (streptococcal sore throat) and with invasive or “flesh-eating” soft tissue infections. We now report that CD44, a hyaluronic acid-binding protein that mediates human cell-cell– and cell-extracellular matrix–binding interactions, functions as a receptor for GAS colonization of the pharynx in vivo. We found that attachment of GAS to murine epithelial keratinocytes was mediated by binding of the GAS hyaluronic acid capsular polysaccharide to CD44. In studies of transgenic mice with a selective defect in epithelial expression of CD44, GAS adherence to CD44-deficient keratinocytes in vitro was reduced compared with adherence to keratinocytes expressing normal levels of CD44. After intranasal inoculation, GAS colonized the oropharynx of wild-type mice but failed to colonize transgenic mice deficient in CD44 expression. GAS colonization of wild-type mice could be blocked by coadministration of mAb to CD44 or by pretreatment of the animals with exogenous hyaluronic acid. These results provide evidence that CD44 serves as a receptor for GAS colonization of the pharynx and support the potential efficacy of disrupting the interaction between the GAS hyaluronic acid capsule and CD44 as a novel approach to preventing pharyngeal infection.

Authors

Colette Cywes, Ivan Stamenkovic, Michael R. Wessels

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GAS pharyngeal colonization of wild-type mice and of mice deficient in e...
GAS pharyngeal colonization of wild-type mice and of mice deficient in expression of epithelial CD44. (a) Histological section through the pharynx of a representative wild-type mouse stained with mAb to CD44. Immunohistochemical staining of the pharyngeal epithelium is seen with mAb to CD44, but not with an irrelevant control mAb. Labels indicate the location of the epithelium (E), lumen (L), and submucosa (S). (b) The left column shows the level of CD44 expression in the pharyngeal epithelium of wild-type and K5-CD44 antisense mice. Histological sections were scored for CD44 expression in the pharyngeal epithelium by three independent observers without knowledge of the throat culture results. CD44 expression was graded on a scale of 1 (background) to 4 (equivalent to wild-type control). On the right are results of throat cultures for GAS on each of 5 days after intranasal inoculation with GAS B514-Sm. (c) Summary of throat culture results presented in b. Data represent the percentage of mice with a positive throat culture on each day after intranasal inoculation for wild-type mice (filled bars), transgenic mice with wild-type levels of CD44 on keratinocytes (hatched bars), and transgenic mice with reduced or absent CD44 expression on keratinocytes (open bars).